Key Topics In Neonatology

The KEY TOPICS Series Advisors: T.M. Craft Department of Anaesthesia and Intensive Care, Royal United Hospital, Bath, UK C.S. Garrard Intensive Therapy Unit,John Radclge Hospital, Oxfoni, UK P.M. Upton Department ofAnaesthetics, Treliske Hospital, Truro, UK Anaesthesia, Second Edition Obstetrics andGynaecology, Second Edition Accident and Emergency Medicine Paediatrics, Second Edition Orthopaedic Surgery Otolaryngology Ophthalmology Psychiatry General Surgery Renal Medicine Ttauma Chronic Pain

Oral and Maxillofacial Surgery Oncology Cardiovascular Medicine Neurology Neonatology Forthcoming titles include: Gastroenterology Respiratory Medicine Thoracic Surgery Critical Care Orthopaedic Trauma Surgery

KEY TOPICS IN

NEONATOLOGY RICHARD H. MUPANEMUNDA

BSc BM MRCP(UK) FRCPCH Honoran, Senior Clinical Lecturer; Birmingham University Consultant Neonatologist, Birmingham Heartlands HospitalNHS Trust Birmingham, UK

MICHAEL WATKINSON MA MB BChir MRCP(UK) FRCPCH Honorary Senior Clinical Lecturer; Birmingham University Consultant Neonatologist, Birmingham Heartlands HospitalNHS Trust Birmingham, UK

Consultant Editor DAVID R. HARVEY MB FRCP FRCPCH Professor of Paediatrics and Neonatal Medicine Honorary Consultant Paediatrician Imperial College Schoolof Medicine, Hammersmith Campus London, UK

BIOS

'SCIENTIFIC PUBUSHERS

Oxford Washington DC

0 BIOS Scientific Publishers Limited,1999 First published 1999 All rights reserved. No part of this book may be reproduced or transmitted, in any form or by any means, without permission.

A CIP catalogue record for this book is available from the British Library.

ISBN 1 85996 256 4

BIOS Scientific Publishers Ltd 9 Newtec Place, Magdalen Road,Oxford OX4 lRE, UK Tel. +44 (011865 726286. Fax. +44 (0)1865 246823 World Wide Web home page: http://www.bios.co.uW Important Note from the Publisher The information contained within this book was obtained by BIOS Scientific Publishers Ltd from sources believed byus to be reliable. However, while every effort has been made to ensure its accuracy, no responsibility for loss or injury whatsoever occasioned to any person acting or refraining from action as a result of information contained herein can be accepted by the authors or publishers.

The reader should remember that medicine is a constantly evolving science and while the authors and publishers have ensuredthat all dosages, applications and practices are based on current indications, there may be specific practices which differ between communities. You should always follow the guidelineslaid down by the manufacturers of specific products and the relevantauthorities in the country in which you are practising.

Production Editor: Jonathan Gunning. Vpeset by J&L Composition Ltd, Filey, UK. Printed by T.J. International Ltd, Padstow, UK.

Front cover:Ashleigh Baldock being caredfor in the Neonatal Intensive Care Unit, Birmingham Heartlands Hospital.

Abdominal distension Acid-base balance Acute collapse Anaemia Anaesthesia and post-operative analgesia" Apnoeas and bradycardias Assessment of gestational age Birth injuries Bleeding disorders Blood glucose homeostasis Blood pressure Bronchopulmonary dysplasia Cardiac arrhythmiasb Childbirth complications and fetal outcome Chromosomal abnormalities Complications of mechanical ventilation Congenital diaphragmatic hernia Congenital heart disease- congestive heart failureb Congenital heart disease- cyanotic defectsb Congenital malformations and birth defects Death of a baby Discharge planning and follow-up Extracorporeal membrane oxygenation Extreme prematurity Feeding difficulties Fluid and electrolyte therapy Gastro-oesophageal reflux Germinal matrix-intraventricular haemorrhage Haemolytic disease Head size Heart murmurs in neonatesb Hepatitis B Herniae Hirschsprung's disease HIV and AIDS Home oxygen therapy Hydrocephalus Hydrops fetalis Hypotonia Hypoxic-ischaemic encephalopathy Immunization Infants of diabetic mothers Infection - general Infection - neonatal

1 3 6 9 13 16 19 21 25 29 34 38 43 46 49 54 57 61 65 70 72 75 78 80 84 87 90 93 97 101 103 105 108

110

114 118 120 122 126 128 132 136 139 143

CONTENTS v

Infection - perinatal Infection - prenatal Inherited metabolic disease - investigation and management Inherited metabolic disease- recognimble patterns Intrauterine growth restriction Intubation Jaundice Jitteriness Liver disorders Maternal drug abuse Mechanical ventilation Meconium aspiration syndrome Multiple pregnancy Necrotizing enterocolitis Neonatal screening for inherited disease Neonatal surgery Neural tube defects Neurological evaluation Neuromuscular disorders - muscular Neuromuscular disorders - neurological Nitric oxide therapy Nutrition Oesophageal anomalies Orthopaedic problems Patent ductus arteriosus Periventricular leucomalacia Persistent pulmonary hypertension of the newborn Polycythaemia Postnatal examination Pregnancy complications and fetal health Prenatal diagnosis Pulmonary air leaks Pulmonary haemohage Pulmonary hypoplasia Renal and urinary tract disorders - nephrology Renal and urinary tract disorders - urology Respiratory distress Respiratory distress syndrome Resuscitation Retinopathy of prematurity Sedation and analgesia on the neonatal intensivecare unit Seizures Sexual ambiguity Shock Skin disorders' Stridor Surfactant replacement therapy

vi CONTENTS

147 151 156 161 165 170 173 177 178 182 185 189 192 195 197 200 203 206 210 214 218 22l 225 227 230 234 237 241 244 247 253 256 259 261 264 270 275 278 282 287 29 I 294 298 302 304 307 309

Surgical emergencies Thermoregulation Trace minerals and vitamins Transfusion of blood and blood products Transport of sick neonates Vomiting

312 315 3 17 323 327 331

Index

333

'Contributed by R. Danha, Senior House Officer in Anaesthetics, Solihull Hospital, Solihull, UK. bConlributed by M. Chaudhari, Specialist Registrar in PaediatricCardiology, The BirminghamChildren's Hospital, Birmingham. UK. 'Contributed by 1I.M. Goodyear.ConsultantPaediatrician,BirminghamHeartlandsHospital NHS Trust, Birmingham. UK.

CONTENTS vi1

ABBREVIATIONS 17-hydroxyprogesterone 17-OHP 25-hydroxyvitamin D 25-OHD 1,25-(OH),D 1,25-dihydroxyvitamin D 3P-hydroxysteroid dehydrogenase 3P-HSD a,-anti-trypsin A,AT abdominal circumference AC angiotensin converting enzyme ACE antidiuretic hormone ADH autosomal dominant polycystic kidney disease ADPCKD alpha-fetoprotein AFT appropriate for gestational age AGA acquired immunodeficiency syndrome AIDS antepartum haemorrhage APH acute respiratory distress syndrome ARDS autosomal recessive polycystic kidney disease ARPCKD atrial septal defect ASD aspartate aminotransferase AST atrioventricular septal defect AVSD blood pressure BP bronchopulmonary dysplasia BPD bovine spongiforrn encephalitis BSE bleeding time BT congenital adrenal hyperplasia CAH cerebral blood flow CBF US Centers for Disease Control and Prevention CDC carbohydrate-deficient glycoprotein CDG congenital diaphragmatic hernia CDH cystic fibrosis CF cyclic guanylate monophosphate cGMP complete heart block CHB congenital heart disease CHD congestive heart failure CHF confidence interval c1 conventional management CM congenital muscular dystrophy CMD cytomegalovirus CMV central nervous system CNS cerebral palsy CP continuous positive airway pressure CPAP citrate, phosphate, dextrose CPD citrate, phosphate, dextrose and adenine CPDA creatine phosphokinase CPK C-reactive protein CRP congenital rubella syndrome CRS

viii ABBREVIATIONS

CSF CT CVH

cvs DA

DCA

ddI DHT DIC DISIDA DMSA DNPH DORV DPPC ECG

ECHO ECM ECMO EDD EDF EEG ELRW ELISA EMG ENT ET FRC FBS FDP

FFP FiO, FL

FRC G6PD GABA GBS GFR GH GOR HBeAg HRIG HBsAg HBV HCV HDN HFJV HFOV

cerebrospinal fluid computerized tomography combined ventricular hypertrophy chorion villus sampling ductus arteriosus dichloroacetate didanosine dihydrotestosterone disseminated intravascular coagulation di-isopropyl iminodiacetic acid dimercaptosuccinic acid dinitrophenylhydrazine double outlet right ventricle dipalmitoyl phosphatidylcholine electrocardiogram echocardiography external cardiac massage extracorporeal membrane oxygenation expected date of delivery end-diastolic flow electroencephalogram extremely low birthweight enzyme-linked immunosorbent assay electromyogram ear, nose and throat endotracheal f u l l blood count fetal blood sampling fibrin degradation products fresh frozen plasma fractional inspired oxygen concentration femoral length functional residual capacity glucose-&phosphate dehydrogenase gamma-aminobutyric acid group B streptococcus glomerular filtration rate growth hormone gastro-oesophageal reflux hepatitis B ‘e’ antigen hepatis B immunoglobulin hepatitis B surface antigen hepatitis B virus hepatitis C virus haemomhagic disease of the newborn high-frequency jet ventilation high-frequency oscillatory ventilation

ABBREVIATIONS ix

HIE

HIV HLHS HNIG HSV ICD ICROP IDM Ig IGF IGFBP i.m.

IMD IPPV IPV

IQ IRT ITP IU IUGR i.v.

IVH IVIG IVS IVU LNAO LBW LCP LGA LIP LP LV LVH MAG-3 MAP MAS MCUG mIU MIS MRI MRSA MSUD mU NEC NICU NIPS NKH NNU

hypoxic-ischaemic encephalopathy human immunodeficiency virus hypoplastic left heart syndrome human normal immunoglobulin herpes simplex virus immune complex dissociation International Classification of Retinopathy of Prematurity infant of diabetic mother immunoglobulin insulin-like growth factor insulin-like growth factor binding protein intramuscular inherited metabolic disease intermittent positive pressure ventilation inactivated poliomyelitis vaccine intelligence quotient immunoreactive trypsin idiopathic thrombocytopenic purpura international units intrauterine growth restriction intravenous intraventricular haemorrhage intravenous immunoglobulin intact ventricular septum intravenous urography left atrial to aortic root ratio low birthweight long-chain polyunsaturated fatty acids large for gestational age lymphoid interstitial pneumonia lumbar puncture left ventricle left ventricular hypertrophy mercapto-acetyl-triglycerine-3

mean airway pressure meconium aspiration syndrome micturating cystourethrogram milli international units Mullerian inhibitor substance magnetic resonance imaging methicillin-resistant Sraphylococcus aureus maple syrup urine disease milli units necrotizing enterocolitis neonatal intensive care unit Neonatal Infant Pain Score non-ketotic hyperglycinaemia neonatal unit

x ABBREVIATIONS

NO NO* NOS

NTD

nvCJD OA

ox OPV OR PaCO, PaO, PAS PRF PCKD PCP PCR PCV PDA PE PEEP PFO PG PHH PI PIE PIP PKU PP PLH PM PNDM p.0. PPHN PROM PS PT

m PUJ PVH

PVL PVR RDA RDS rHuEP0 ROP RSV RSVTG RT

nitric oxide nitrogen dioxide nitric oxide synthase neural tube defect new variant Creutzfeldt-Jakob disease oesophageal atresia oxygenation index oral poliomyelitis vaccine odds ratio arterial carbon dioxide tension arterial oxygen tension periodic acidSchiff reaction pulmonary blood flow polycystic kidney disease Pneumocystis carinii pneumonia polymerase chain reaction packed cell volume patent ductus arteriosus pre-eclampsia positive end-expiratory pressure patent foramen ovale prostaglandin post-haemonhagic hydrocephalus protease inhibitor pulmonary interstitial emphysema peak inspiratory pressure phenylketonuria platelet AI antigen pulmonary lymphoid hyperplasia post-mortem permanent neonatal diabetes mellitus by mouth persistent pulmonary hypertension of the newborn preterm rupture of membranes pulmonary stenosis prothrombin time partial thromboplastin time pelvi-ureteric junction periventricular haemorrhage periventricular leucomalacia pulmonary vascular resistance recommended dietary allowance respiratory distress syndrome recombinant human erythropoietin retinopathy of prematurity respiratory syncytial virus respiratory syncytial virus immunoglobulin reptilase time

ABBREVIATIONS xi

RTA RVH SaO, S.C.

SCD SCID SGA sGC SLE SMA sPDA

SRY SVT TA-GVHD TAPVD TAR TB TDF Te TGA THAM

Ti TMI TNDM TOF TORCH TPN TPHA TRH TSH 'IT

U&E UAC UDPGT UTI

uvc vcv

VDRL VKDB VLBW VSD VT VUR

vzv

VZtG W C WPW ZDV

renal tubular acidosis right ventricular hypertrophy oxygen saturation subcutaneous sickle cell disease severe combined immunodeficiency small for gestational age soluble guanylate cyclase systemic lupus erythematosus spinal muscular atrophy symptomatic patent ductus arteriosus sex determining region Y supraventricular tachycardia transfusion-associated graft-versus-host-disease total anomalous pulmonary venous drainage thrombocytopenia with absent radius tuberculosis testis-determining factor expiratory time transposition of great arteries tris-hydroxymethyl-aminomethane inspiratory time transient myocardial ischaemia transient neonatal diabetes mellitus tracheo-oesophageal fistula toxoplasmosis, other (particularly syphilis), rubella. cytomegalovirus, herpes total parenteral nutrition Treponima pallidumhaemagglutination assay thyrotrophin-releasing hormone thyroid-stimulating hormone thrombin time urea and electrolytes umbilical artery catheter undine diphosphate glucuronyl transferase urinary tract infection umbilical venous catheter volume controlled ventilation venereal disease research laboratory vitamin K deficiency bleeding very low birthweight ventricular septal defect ventricular tachycardia vesico-ureteric reflux varicella-zoster virus varicella-zoster immunoglobulin white blood cell Wolf-ParkinsowWhite syndrome zidovudine

xi1 ABBREVIATIONS

Neonatology is a relatively new subspecialty in medicine, having largely come into being in the last three decades. This shortperiodhas,however, witnessed a dramatic reduction in neonatal mortality, particularlyof very small preterm infants, due to the rapid advances in perinatal and neonatal medicine. Many areas of neonatology are still changing asnew information becomes available, often leading to new diagnostic and therapeutic techniques. Although large formal neonatology textbooks serve as a very useful resource, they soon becomedated as new information becomes available. This book aims to provide the reader with a very up-to-date summary of the current concepts and practices in neonatal medicine. The field is covered in a series of self-contained, easily read topics set in a unique format which encourages the adoption of a problem-based approach ideal for day-to-day clinical practice. Although some topics reflect our personal clinicalpractice,the systematic approach to each topic is retained. Reference ismade to related topics whichallows the reader ready access to the subject matter of their choice unencumbered by extraneous detail. As such, the text isan ideal revision aid for the neonatology components of the postgraduate paediatric examinations (including MRCP or DCH). It will also serve as a useful refcrence text for other professionals, both trainees and qualified, who are involved in the care of both well and sick newborns. We are thankful to our colleagues for reading through various topics. in particular Dr R. Danha who readthrough most of the topics and was a source of great encouragement. Also our sincere appreciation to Tracey Fantham whose secretarial assistancemade this book possible. Finally, we are especially thankful to the staffat BIOS for their helpful guidance from the outset, and their enduring patience despite the many broken deadlines. We dedicate the book to our own 'ex-prems' Francesca, Grace and Henry. Richard H. Mrrpanernunda Michael Watkinson

PREFACE xiii

This Page Intentionally Left Blank

Abdominal distension is one of the commonest physical signs for which a medical opinion may be sought. The causes are legion,varyingfromphysiologicalabdominaldistension through a variety of benign causesto serious acute medical emergencies. Aetiology

1. Physiological Gaseous distension in infants receiving mechanical ventilation or continuous positive airway pressure (CPAP). m Delayed bowel action. m Lax abdominal muscles (e.g. prune belly syndrome). m Urinary retention.

m

m m m

Pathological Ascites. Hirschsprung’s disease. Intestinal obstruction (e.g. atresia or volvulus). Intra-abdominal masses (organomegaly or tumours). Iatrogenic (e.g. intraperitoneal extravasation of parenteral infusates). Intra-abdominal haemorrhage. Imperforate anus. Meconium ileus or plug (associated with cystic fibrosis

m m

Necrotizing enterocolitis (NEC). Pneumoperitoneum.

(CF)).

Presentation

This may be the sole abnormal physical sign in an otherwise well infant when physiological causes are responsible. On the otherhand,pathologicalabdominaldistensionwith bilious vomiting may present at birth or later in a sick infant with a shiny, silent, tense and tender abdomen with perforated NEC. In non-ventilated infants, this may be heralded by apnoeas and bradycardias or acute collapse. A ventilated infant witha rapidlyincreasingabdominal girth mayhavedevelopeda pneumoperitoneum.

Investigations m m

Management

Abdominal radiograph. Abdominalultrasoundscan. Water-soluble contrast or barium enema study. Infectionscreen. Electrolytes.

Infantspresentingwithmeconium ileus or thosepassinga meconium plug should be screened for CF (immunoreactive trypsin (IRT)or DNA analysis for common CF mutations). Acute and subacute intestinal obstruction is managed by gastric decompression (nasogastric suction) and elective surgery

ABDOMINAL DISTENSION l

in anappropriate centre. The infant should be ina stable condition prior to surgery. Infants with severe or perforated NEC may require more urgentsurgical intervention and should receive adequate analgesia, broad-spectrum antibiotics including anaerobic cover (e.g. ceftazidime, vancomycin and metronidazole) and, if necessary, mechanicalventilation. Intraabdominal collections (e.g.ascites) may be drained with afine canula to decompress the abdomen, and the peritoneal fluid cultured. Adequate analgesia should always be administered where the infant may be in pain (e.g. i.v. morphine infusion at 20-40 kglkglhour foran infant with perforated bowel).

Further reading Beasley SW, Hutson J M ,Auldist AW. Essential Paediatric Surgery.London: Arnold, 1996. Black JA, Whitfield M E Neonatal Emergencies: Early Detection and Management,2nd edn. Oxford: Ruttenvorth-Heinemann, 199 1. O'Doherty N. Atlas ofthe Newborn, 2nd edn. Lancaster: MTP Press, 1985. Philip AGS. Neonntologv: A Practical Guide, 4th edn. Philadelphia: W.B. Saunders, 1996. Reyes HM, Vidyasagar D (eds). Neonatal surgery. Clinics in Perinatology, 1989; 16 1.

Related topics of interest Anaesthesia and post-operative analgesia (p. 13) Feeding difficulties (p. 84) Hirschsprung's disease (p. 110) Necrotizing enterocolitis (p. 195) Neonatal surgery (p. 200) Vomiting (p. 331)

2 ABDOMINAL DISTENSION

The acid-base balance is a vital dynamic index of aninfant's wellbeing. The pH of plasma is 7.36-7.45 (33-44 nmolA of H '). An infant is acidotic if the pHis c7.26 and alkalotic if the pH is >7.46. If the pH is 7.46 with a low carbon dioxidelevel, a respiratory alkalosis is present (e.g. hyperventilation) and if the carbon dioxide level is normal, a metabolic alkalosis is present. Metabolic and respiratory alkalosis is uncommon and invariably iatrogenic (excess base administrationor hyperventilation). Acidosis, on the other hand, is quite common and maybe respiratory (high carbon dioxide), metabolic (lowor normal carbon dioxide)or mixed (combinationof both) with a negative base excess. The causes and management of these conditions are detailed in Table I below. There are several buffering systems in place to prevent the build up of excess acid (especially bicarbonate, haemoglobin, protein and phosphate). These systems are not fully developedinnewbornsand particularly preterm infants. There is atendency, therefore, for newborns to develop acidosis (most commonly mixed acidosis). Excess acid maybe generated from ongoing metabolic processes (including congenital metabolic errors of metabolism), enteral or parenteral intake, respiratory failure, decreased renal excretion of acid or the inap propriate renal loss of bicarbonate. The acid-base balance is best assessed by arterial blood gas analysis. When metabolic acidosis is present,it is important to identify the cause in order to give the specific therapy for it. A raised anion gap suggests the presence of an unmeasured organic acid (e.g. lactate). The anion gap is calculated as the sum of sodium and potassium, less the sum of chloride and bicarbonate (normal value:6-14 mmolfl).

Table 1. Causes and management of alkalosis and acidosis Condition Respiratory alkalosis

Hyperventilation

Reduce ventilatory supportif ventilated

Respiratory failure Endotracheal tube blockage (raised PaC02. normal or low PaO,) Endotracheal tube dislodged (raised PaCO,, low PaO,)

Intubation and ventilation

Respiratory acidosis Unventilated Ventilated

Metabolic alkalosis

Metabolic acidosis

Change endotrachealtube

Re-intubate

Pneumothorax (raised PaCO,, and low PaO,)

Aspirate pneumothorax and insert chest drain

Excessive gastric losses, e.g. high atresia, pyloric stenosis

Replacement of gastric losses

Excess base administration

Stop base administration Administer oxygen 2 intermittent positivepressure ventilation (IPPV)

Hypoxia, anaerobic metabolism

ACID-BASEBALANCE

3

Table 1. (continued) Condition Blood transfusion

Metabolic Anaemiaacidosis Excessive respiratory effort

IPPV

Hypotension and hypovolaemia

Colloid administration +. inotropes

Renal bicarbonate loss Excess acid administration parenterally

Bicarbonate replacement

Infection

Broad-spectrum antibiotics after all appropriate cultures Assay serum amino acids, lactate and ammonia, with urinalysis for pH, acetone, ketoacids and urine amino and orrzanic acids

Inborn error of metabolism (persistent acidosis)

Problemsassociatedwith marked acidosis

0

0

Baseadministration

Reduce intake appropriately

Increased pulmonary vascular resistance. Inhibition of surfactant synthesis. Impaired myocardial contractility. Impaired diaphragmatic contractility. Impaired renal excretion of acid load.

First check thattheblood gases make sense and repeat if necessary, as excessheparin in a blood gas syringe may give e r r e neous readings. Administer base when the pH is ~ 7 . 2 and 5 the base deficit is greaterthan - 10mmoyl. The amount of base (in mmol) is calculatedfrom the formula: base deficit (mmoyl) X bodyweight (kg) X 0.4 (extracellular volume). Give bicarbonate as a 4.2% solution (0.5 mmoYml of solution) as a slow infusion (0.5 mmohin). In the presence of a high PaCO, or hypernatraemia, THAM (tris-hydroxymethylaminomethane) may be preferable. A 7% THAM solution contains 0.5 mmoYml. THAM, however, may cause apnoeas and should preferably be administered to ventilated infants. It is preferable to initially administer an amount of base sufficient to only half correct the calculated base deficit, with repeat gases to reassesstheacid-base balance. For persistentacidosis a constant infusion of base may be required.

Problems associated with base administration

4 ACID-BASE BALANCE

Provided appropriate doses of base are administered slowly, concerns regarding intracerebral haemorrhage associated with base administration may be allayed. However, over-correction

of a metabolic acidosis may carry morerisks than a persistent mild acidosis. Thus some patients with urea cycle defects may present with mild acidaemia, which should not be corrected as acidosis protects against NH, dissociation and toxicity.

Common patternsof blood gas abnormalities

pH and corresponding [H'] hydrogen ion concentration

Respiratory alkalosis (acute): pH raised. PaCO, reduced, HC03 normal or slightly reduced. Respiratory alkalosis (chronic): pHnormal or raised, PaCO, reduced, HC03 reduced. Respiratory acidosis (acute): pH decreased, PaCO, raised, HC03 normal or slightly raised. Respiratoryacidosis (chronic): pH slightly decreased, PaCO, raised, HCO, raised. Metabolic acidosis: pHreduced, PaC02 reduced, HC03 reduced. Metabolic alkalosis: pH raised, PaCOt raised or normal, HCO, raised. PH 6.9 7.0 7.1 7.2 7.3

(nanomolar) 100

1.4

40

7.5 7.6

25

Further reading Driscoll P, Brown T, Gwinnut C. Wardle T.A Simple Guide to Blood Gas Analysis. London: BMJ Publishing, 1997. Howell JH. Sodium bicarbonate in the perinatal setting revisited. Clinics in Perinatology, 1987; 14: 807-16.

Sen I. Regulation of acid-base balance in thefetus and neonate. In: Polin RA, Fox WW (eds). Fetal and Neonatal Physiology, 2nd edn. Philadephia: W.B. Saunders, 1998; 1726-30. von Planta I, Weil MH, von Planta Met al. Hypercarbic acidosis reduces cardiacresuscibility. Critical Care Medicine. 1991; 19: 1177-82.

Related topics of interest Inherited metabolic disease - investigation and management (p. 156) Mechanical ventilation (p. 185) Resuscitation (p. 282) Shock (p. 302)

ACID-BASE BALANCE 5

ACUTE COLLAPSE This is one acute medical emergency where swift and appropriate response can make a major difference to outcome. Irrespective of the cause, the major objectives should be to re-establish adequate gas exchange and maintain the cardiovascular circulation.

Aetiology

0 0 0 0

0

0 0

0

Presentation

0 0 0

0

0 0 0

6 ACUTE COLLAPSE

(*

Sudden onset of bradycardia. hypotension, pallor or cyanosis in either a previously wellor already unwell infant. There may, in addition, be vomitus in the mouth, blood coming from the oropharynx or trachea, abdominal distension and hypothermia. The infant may look extremelyill with laboured or absent respiratory effort, mottledskin.markedhypotoniaandcold peripheries. Bloody stools may be passed at the same time. suggestingintra-abdominalpathology(NEC).Occasionally seizures may also be noted.

Investigations

Management

Overwhelming sepsis. Pneumothorax. Aspiration of vomitus. Major haemorrhage (e.g. intra-abdominal, intrapulmonary or intracranial). Severe NEC perforation). Metabolic and endocrine disorders. Congenital heart disease (e.g. hypoplastic left heart syndrome, interrupted aortic arch). Compromised airway in the ventilated infant (blocked or displaced endotracheal tube).

Fibreopticcold light chesttransillumination for pneumothoraces. Chestandabdominalradiographs. Arterial bloodgases. Bloodglucose. Ureaand electrolytes (WE). Full bloodcount(FBC). Clottingscreen. Headultrasoundscan. Infection screen (blood, urine +cerebrospinal fluid (CSF)). Metabolicscreen(obtainacutebloodandurinesamples and store accordingly).

Near normal gas exchange, adequate tissue perfusion and normalpressureshould be re-establishedandmaintained as rapidly as possible. If the respiratory effort is inadequate and the infant is not already ventilated, clear the oropharynx and commence bag and mask (or T-piece) ventilation with 100% oxygen. Check pulse and peripheral pulses. If absent,commence external cardiac massage (ECM). If the infant is unresponsive

after 1 min. intubate and continue ECM with bagging. Ensure that the bag and maskor T-piece set-up is connected to oxygen and that it is turnedon!Transilluminatethechestwall to exclude a large tension pneumothorax and drain (needle aspiration) if present. If still unresponsive, check the endotracheal tube position and administer 0.3ml of 1:lOOO adrenaline via the endotracheal tube. If this produces asatisfactory response in the pulseandoxygenation(saturations >95%), discontinue ECM and continue with respiratory support and connect to a mechanical ventilator. Check arterial blood gases and blood glucoseandadjust ventilation accordingly.Givedextrose andor base as required. Obtain chest and abdominal X-rays. Administercolloidiftheperipheral circulation is inadequate, followed, if necessary, by inotropes (dopamineor dobutamine at 5-20vcg/kg/min). Once the infant is stable, work out the mostlikely cause, if it is not already evident. Consider performing a head ultrasound scan in a newborn where intraventricular haemorrhage(IVH)might be a possibility. If a haemorrhage has occurred, checkclotting and administer fresh frozen plasma (FFP) or cryoprecipitate (if fibrinogen 5 mmolA)and -t hypoglycaemia are present.Maintainrespiratorysupport with full monitoring over several hours and gradually wean according to the status of the infant and results ofthe investigations. If an infant remains unresponsive to full cardiopulmonary resuscitation for 4-5 min, give 1:lOOO adrenaline (0.4-1 ml i.v.) and consider giving base if the resuscitation efforts are still unsuccessful after 10min (3-5mmol of 4.2%NaHCO, i.v.).Needleboth sides of the chest in case bilateral pneumothoraces are present. Continue withresuscitation efforts for at least 20 min.

Unsuccessful resuscitations

Alwaystryandobtainconsent for apost-mortem(PM).A coroner may need to be informed. Where inherited metabolic disease is a possibility, obtain urine (amino and organicacids), blood (amino acids, DNA studies). skin (fibroblast cultures), muscle and/orliver biopsies. Freeze urine, spin blood, and s e p arate red cells and plasma and freeze separately. Snap freeze liver and muscle samples in liquid nitrogen or store at 4°C in tissue culture medium or plain saline, but transfer to the most appropriate storage medium at the earliest opportunity.

ACUTE COLLAPSE 7

Further reading American Academyof PediatricslAmerican Heart Association.Texrbook of Neonatal Resusciration. Dallas: American Heart Association, 1994. Black JA. Whitfield ME Neonatal Emergencies: Earlv Detection and Management, 2nd edn. Oxford: Butterworth-Heinemann, 1991. Burchfield DJ, Berkowitz ID,Berg RA et al. Medications in neonatal resuscitation. Annals of Emergency Medicine. 1993; 22: 435. Emery L, Variend S, Howat AJ er al. Investigation of inborn emors of metabolism in unexpected infant deaths. Lancer, 1988; ii: 29. Meerstadt PWD. GyllC. Manual of Emergency X-ray Interpretation. Philadelphia: W.B. Saunden, 1995. Reece RM (ed). Manual of Emergency Pediatrics, 4th edn. Philadelphia: W.B. Saunders, 1992. Surtees R, Leonard JV. Acute metabolic encephalopathy: a reviewof causes, mechanisms and treatment. Journal of Inherited Metabolic Disease, 1989; 12: 42. Willett LD, Nelson Rh4 Jr. Outcome of cardiopulmonary resuscitation in the neonatal intensive care unit. Critical Care Medicine, 1986; 14: 773.

Related topics of interest Acid-base balance (p. 3) Inherited metabolic disease - investigation and management (p. 156) Pulmonary haemorrhage (p. 259) Resuscitation (p. 282) Shock (p. 302)

8 ACUTE COLLAPSE

The cord haemogloblin concentration in term infants averages 17g/dl (range 14-20g/dl) and 14g/dl (range 13-18g/dl) in preterm infants. Delayed clamping of the cord and holding the infant below the level of the placenta at birth will significantly raise thehaemoglobin concentration. After birth, erythropoietin production is switched off by the greater availability ofoxygen, reticulocytosis falls from 5% (at birth) toless than !% and the haemoglobin level falls to a nadir of 7-10g/dl by 8-10 weeks, remaining stable for several weeks, before gradually increasing. The fall in haemoglobin is more rapid and more marked in preterm infants, with the nadir of haemoglobin concentration varying inversely with gestational age. In terminfants this decline and rise in haemoglobin concentration has been labelled physiological as the infants are asymptomatic. In preterm infants the fall in haemoglobinconcentration is often so marked that some infants require erythrocyte transfusions and thus this 'anaemia of prematurity' is labelled non-physiological. It is characterized by reticulocytopenia, bone marrow hypoplasia and erythropoietin levels thatare low relative to the degree of anaemia. Anaemia may present at birth or during the first week of life (early anaemia), or later (later onset anaemia),depending on the aetiology. Anaemia presenting after thefirst day oflife commonly follows haemorrhage or haemolysis (non-immune), while the anaemia due to impaired red cell production often presents after the first month of life.

Early onset anaemia This is a haemoglobin level of 30min). 0 Pallorandsweatingwithfeeding. 0 Breathlessness and irritability during feeding. 0 Failure to gainweight. 0

2. Physical examination

(a) Signs of impaired myocardial function and compromised tissue perfusion 0 Tachycardia (heart rate >150/min),galloprhythm,weak and thready pulse. 0 Cardiomegaly (clinical andradiographic). 0 Reduced urine output (3s), increased toe-coretemperaturedifference(>2"C),andimpalpable pulses. (b) Signs of pulmonary congestion Tachypnoea (respiratory rate %O/min). 0 Subcostal or intercostal recession. 0 Wheezing or basal rales. 0 Cyanosis. 0 Wet lung fields on chest X-ray. 0 Frankpulmonaryoedema. (c) Signs of systemic venous congestion 0 Hepatomegaly (>3cm or progressive). Excess weight gain (>30g/24hours) despite feeding difficulties.

Differential diagnosis of neonates inCHF

I . Non-cardiac causes Asphyxia. 0 Septicaemia. 0 Anaemia. 0 Polycythaemia. 0 Hypoglycaemia. 0 Fluid overload. 0 Arteriovenous fistulae.

0

-

CONGENITAL HEART DISEASE CONGESTIVE HEART FAILURE61

2. Cardiac causes (a) Left ventricular outflow tract obstruction Hypoplastic left heart syndrome (HLHS). Critical aortic stenosis. Coarctationofthe aorta. 0 Interrupted aortic arch. 0

Neonates with these conditions are usually normal at birth, as systemic perfusion and pulses are maintained by the patent ductus arteriosus (PDA).Cardiac failure andcardiogenic shock sets in with postnatal constriction of the ductus a. systemic and coronary perfusion is impaired. Severe heart failure is usually seen in the first week of life. ’

(b) Left-to-right shunts 0 0

0 0

LargePDA. LargeVSD. Truncus arteriosus. Atrioventricular septal defects(AVSD). Total anomalous pulmonary venous connection (nonobstructed).

Presentation is beyond the first week of life as pulmonary vascularresistance falls. Features of increasedpulmonary blood flow and sympathetic over-stimulation are predominant. (c) Structurally normal heart with left ventricular dysfunction Cardiacarrhythmias. TMI ofthenewborn. 0 Cardiomyopathies (infective. storage disorders. endocardial fibroelastosis, infant of diabetic mother).

Evaluation of a neonate with CHF

1. Perform the

A-B-C of neonatal cardiopulmonary resuscitation. 2. Correct electrolyte and acid-base abnormalities. 3. Excludenon-cardiaccauses. 4. Determine possible underlying cardiac aetiology and mechanism of CHF. A schematic representation of with CHF is given in Figure I :

the evaluation of an infant

62 CONGENITAL HEART DISEASE- CONGESTIVE HEART FAILURE

Congestive Heart Failure

With shock (medical emergency)

I

J

4

II I

I

I

I

Onset lweek of life SignsofpulmonaryovercirculationSignsofpoorperfusion.weak

I

I I

I

I

I

4 Left-to-rightshunts

4

I

1

I

I I

I

I

l

or unequalpulses

t LV outflow tract obstruction

t

l

I I

Sounding pulse Large PDA Truncus arteriosus

Coarctation of aorta Weak or absent femoral pulses ECG: LVH

TVpical murmur Large PDA Large VSD UnobstructedTAPVD AVSD

Hypoplastic leflheart syndrome Weak or absent brachial and femoral pulses Cyanosis (obligatory R>L atrial shunt) ECG: right axis, RVH, paucity of LV forces Critical aortic stenosis Weak or absent brachial and femoral pulses ECG: LVH with strain pattern Interrupted aortic arch Unequal brachials orweak femoral pulses RVH

ECG: restriction 1. Fluid 2. Ensure adequate calorie intake 3. Diuretics: Frusemide 1 mgkgldose Amiloride 0.1 rng/kg/dose

I

Echo for anatomical diagnosis

I

1. Ventilatory support 2. PGE, or PGEI infusion 3. Correct metabolic acidosis 4. Human albumin: 5-10mVkg for shock 5. Dobutarnine 510pg/kg/min 3-5pg/kg/min 6. Dopamine

TruncusarteriosuflAPVD Early surgical repair VSDffDNAVSD Optical medical therapyto control CHF

Transfer to specialist cardiac unit for urgent echocardiogram and surgical intervention I

Early surgeryif medical therapy fails: Failure to thrive Persistent heart failure Development of pulmonary hypertension

Figure 1. Schematic representation of the evaluation of an infant withCHF.

CONGENITAL HEART DISEASE- CONGESTIVE HEART FAILURE63

Further reading Burton DA, Cabalka AK. Cardiac evaluation of infants. Pediatric Clinics of North America, 1994; 41: 991-1011. Castaneda AR,Jonas R A , Mayer E,Hanky FL. Cardiac Surgery of the Neonate and Infant. Philadelphia: W.B. Saunders, 1994. Park MK. Pediatric Cardiology for Practitioners, 3rd edn. Chicago: YearBook Medical Publishers, 1996. Silove ED. Assessment and management ofcongenital heart disease in the newbornby the district paediatrician. Archives of Disease in Childhood, 1994; 70: F71-4. Snider AR, Serwer GA. Echocardiographv in Pediatric Heart Disease.St. Louis: Mosby Year Book, 1990.

Related topics of interest Acute collapse (p.6) Cardiac anythrnias (p. 43) Congenital heart disease - cyanotic defects (p. 65) Heart murmurs in neonates (p. 103) Shock (p. 302)

64 CONGENITAL HEART DISEASE - CONGESTIVE HEART FAILURE

CONGENITAL HEART DISEASECYANOTIC DEFECTS The incidence of congenital heart disease (CHD) is about 8 per lo00 live births andone-third of these cases present in the neonatal period. The common modes of presentation are: 0 0

Cyanosis. Heartmurmur. Congestive cardiac failure/vascular collapse. Cardiac arrhythmias.

Symptomatic heart disease in the neonate presents as cyanosis, cardiac failure or cardiovascular collapse. Asymptomatic heart disease is usually diagnosed when incidental findingof a heart murmur, abnormal pulses or abnormal heart rhythm leads to detailed cardiac evaluation. Routine cardiac screening in cases of various dysmorphic syndromes, chromosomal abnormalities or congenital abnormalities of the gastrointestinal tract also enablesearly diagnosis of asymptomatic heart disease. The initial evaluation should be aimed at the recognition of the cardiac problem and its severity, followed by stabilization of the neonate for safe and timely transfer to a specialist cardiacunit.

Cyanotic heart defects Cyanosis refers to blue discoloration of the skin and the mucous membranes due to presence of more than 4-5 g/dl of reduced haemoglobin in circulation. Clinically it usually is apparent at oxygen saturations of 85% or below. It is one of the most significant signs of serious cardiac abnormality and hence prompt recognition and diagnostic evaluation is mandatory. Central cyanosis results from arterial desaturation or abnormal haemoglobin andaffectsthe tongue, mucous membranes and peripheral skin.Peripheral cyanosis results fromprolongation ofthe circulation time and an increase in tissue oxygen extractionandis confined to the extremities. Itis typically seen in neonates with poor cardiac output, sepsis, polycythaemia or metabolic acidosis. The arterial oxygen saturation and PaOzis normal in peripheral cyanosis. Differential cyanosis (lower limbs >> upper limbs) is seen in neonates with right-to-left ductal shunting associated with PPHN or an aortic arch obstruction. Reversed differential cyanosis (upper limbs >> lower limbs) is seen in the setting of ventriculoarterial discordance and right-to-left ductal shunting.

Features of cyanosis due to CHD

0

0

Central cyanosis with minimal respiratory distress. Worsening of cyanosis with crying/agitation. Differentialcyanosis, Arterial blood gas analysis: low PaO, with normal PaCO,. No response to challenge with 100% inspired oxygen (hyperoxia test). Abnormalities on cardiovascular examination: precordial hyperactivity, heart murmur, unequal peripheral pulses. Chest radiograph: abnormal cardiacsizelshape, abnormal pulmonary vascularity.

CONGENITAL HEART DISEASE- CYANOTIC DEFECTS 65

AbnormalECG(normalECG does notexcludeserious cardiac abnormality in neonates). The mostimportant differential ofcardiaccyanosis is cyanosis due to respiratory disorders whichis accompanied by signs of respiratory distress. It is also characterized by CO, retention on blood gas analysis. qpically in response to 1 0 0 % inspired oxygen the saturations improve and PaO, is raised to >lSOmmHg (20kPa). In addition there is evidence of parenchymal lung disease on chest radiograph. Rarely, both the pulmonaryandcardiaccomponentsmaycontribute to cyanosis, as seen in obstructed anomalous pulmonary venous connection,withpulmonaryoedemamakingthe distinction more difficult.

Initial evaluation Investigations

0

0

Monitoring

FBC - check haemoglobin. white cell count, platelets and markers of sepsis. Biochemistry - urea, creatinine, electrolytes, calcium, blood glucose. Chest radiograph - heart sizelshape, pulmonary vascularity (NILIT). ECG - note cardiac rhythm, QRS axis, ventricular hypertrophy (right/left/both). Blood gases - arterial sample from the right radial or temporal arteries to avoidthe effect of right-to-left ductal shunt. Additional post-ductal arterial sample from lower limb in caseof differential cyanosis.Capillarysamples from a warmed heel canbe reliably used for estimation of acidosis and PaCO,. Hyperoxia test - measurementof arterial blood gas tensions and pHin room air and after administration of 100% oxygen for 5-10min aids in the differential diagnosis of central cyanosis. Little or no change in oxygen tension is suggestive of cyanotic heartdisease. PaO, >>20kPa makes it less likely and PaO, >>30kPa excludes cyanotic CHD.

Careful monitoring of the following parameters is mandatory during stabilization and transfer: 0

0

0 0

Bodytemperature(toe-core differential). Respiratory rate and pattern. Heart rate andrhythm. Blood pressure. Oxygensaturationbypulseoxymetry. Blood gases with electrolytes, blood glucose. Urineoutput.

66 CONGENITAL HEART DISEASE - CYANOTIC DEFECTS

The ABCDof neonatal cardiopulmonary resuscitation is:

Stabilization

Airway. Secure airway; monitor for apnoeas if airway is not secured. Breathing.Ventilatorysupport in presenceofpulmonary oedema or persistent acidosis. Circulation. Volume expansion (5-10mlkg of 4.5% human albumin) if hypovolaemic. Drugs.

1. To ensure ductalpntency. Prostaglandin E, or F1 infusion. Recommended dilution: 500pg in 500ml of 5% dextrose, i.e. 1pg/ml. Starting dose: 0.3 mVkglhour = 0.005 pgkgl min.Doublethe dose in 20 min if SaO, is unchanged. Apnoea is a recognized side-effect.

2. Correction of metabolic acidosis. Sodiumbicarbonate: half correction, dose guided bythe base dcficit.

3. Inotropic support. Dobutamineinfusion

(5-10 pgkgl

min) via peripheral i.v. canula.

4. To improve renal pelfusion. Dopamine infusion (3-5 pgl kglmin) via central venous canula. 5. Diuretics. Frusemide 1 mgkg i.v. if in cardiac failure (but not circulatory failure!) to reduce the increased extravascular fluid volume.

Differential diagnosis of cyanotic CHD in neonates CHD with decreased pulmonary blood flow

CHD withnormal or increasedpulmonary blood flow Structurally normal hearts with right-to-left shunts

Lesions characterized by obstruction to pulmonary blood flow (PBF)with right-to-left shunt at atrial or ventricular level (see Figure I ) . Transpositionofgreat arteries (TGA)is thecommonestlesion of this type in neonates(see Figure 2).

I . Persistent pulmonary hypertension of thenewborn (PPHN). In thiscondition.thenorma1fallin pulmonary vascular resistance at birth is delayed. This results in persistence of pulmonary hypertension which leads to a right-to-left shunt through the patentductus arteriosus and foramen ovalecausing arterial desaturation. Right-to-left ductal shunt results in typical differential cyanosis (lower limbs>> upper limbs), whereas predominantly atrial shunt results ingeneralized central cyanosis,making distinction from structural heartdisease more difficult. Association with precipitating conditions like meconium aspiration, perinatal asphyxia or sepsis, and increase

CONGENITAL HEART DISEASE- CYANOTIC DEFECTS 67

. $ CVH Univentricular heart with PA or pulmonary atresia Truncus arteriosus with hypoplastic PAS

Tetralogy of Fallot Pulmonary atresia, VSD Pulmonary atresia, IVS Severe PS Ebstein's anomaly TGA-VSD-PS DORV-VSD-PS L

LVH Tricuspid atresia (left axis deviation) Pulmonary atresia, IVS (normal axis: +30 to +90)

J

Figure 1. CHD with decreased pulmonary blood flow.

CENTRAL CYANOSIS+ CHEST X-RAY TI' PBF (heart failure andlor respiratory distress)

J

Truncus arteriosus Hypoplastic left heart

Tricuspid atresia with large VSD and TGA

Figure 2. CHD with increased pulmonary blood flow. in the post-ductal PaO, in response to hyperventilation causing hypocapnia and respiratory alkalosis, helps distinguish PPHN from structural heart defects. Echocardiographic evaluation is essential to confirm structurally normalheart with right-to-left ductal and/or atrial shunt.

2. Transientmyocardialischaemia(TMI). This condition i s characterized by ischaemic myocardial dysfunction and presents either with cyanosis or with congestive cardiac failure and a low output state. Preceding history of perinatal hypoxia and/or hypoglycaemia i s common. Right-to-left atrial shunt results in central cyanosis and global myocardial dysfunction 68 CONGENITAL HEART DISEASE- CYANOTIC DEFECTS

causing heart failure. The condition may co-exist with PPHN. The ECGshowsischaemic S-T andT-wavechanges (S-T depression and T-wave inversion) and at times anterior or inferior infarct patterns. Echocardiography reveals dilated poorly contractile left and right ventricles with right-to-left atrial shunt on colour Doppler. Treatmentis supportive and aimedat controlling heart failure.

Further reading Anderson R, Baker E, Rigby M, Shinebourne E, Tynan M (eds). Pediatric Cardiology, 2nd edn. Edinburgh: Churchill Livingstone, 1998. Burton DA, Cabalka AK. Cardiac evaluation of infants. Pediatric Clinics of North America,

1994;41: 991-1011. FreedomRM,Benson LN, Smallhorn JF. NeonatalHeart Diseuse. New York SpringerVerlag, 1992. Park MK. Pediatric Cardiologyfor Practitioners, 3rd edn. Chicago: Year Book MedicalPublishers, 1996. Silove ED. Assessment and management of congenital heart diseasein the newborn by the district paediatrician. Archives of Disease in Childhood, 1994:70: F71-4. Snider AR, Sewer GA. Echocardiography in Pediatric Heart Disease. St. Louis: Mosby Year Book, 1990. Stark J,de Leva1 M (eds). Suqery for Congenital Heart Defects,2nd edn. Philadelphia:W.B. Saunders, 1994.

Related topicsof interest Acute collapse (p. 6) Cardiac arrhythmias (p. 43) Congenital heart disease - congestive heart failure (p. 61) Heart murmurs in neonates (p. 103)

-

CONGENITAL HEART DISEASE CYANOTIC DEFECTS 69

CONGENITAL MALFORMATIONS AND BIRTH DEFECTS The assessment of a dysmorphic newborn infant requires a systematic approach in order to make a correct diagnosis, implement appropriate management and provide theparents with an accurate prognosis and appropriate genetic counselling. Congenital malformations are present in approximately 2.5% of the general population. Most of these occur as single minor abnormalities but they occur with increased frequency in infants with other major malformations. Certain definitions are important at the onset.A birth defectis afault or disorder present or arising at birth. A malformation arises during embryonic life as an abnormal developmental process. A deformation is a mechanical alteration in the form or shape of a part of the body with previous normal development (e.g. talipes). A disruption is an interruption of normal development resulting in destruction of the body part (e.g. limb loss from amniotic band). A single insult that results in a cascade of secondary consequences is a malformation sequence. If an insult causes multiple defects not causally related, the termmalformations syndrome may be used. A syndrome is a pattern of malformations thought to be pathogenically related. An association is a non-random Occurrence of several anomalies not known to be a syndrome or sequence. Malformation syndromes may be chromosomal, inherited or environmentally induced, whereas disruptions and deformations rarely have a genetic basis.

Clinical approach

Obtain a detailed history: Family history of malformations with a geneticbasis. Parental consanguinity (autosomal recessive disorders). Multiple miscamageslstillbirthths. Elderly mother. Exposure to alcohol, drugs, radiation and infection during pregnancy. Oligo- or polyhydramnios. Prolonged premature rupture of membranes. Intrauterine growth restriction. Reduced fetal movements (? neuromuscular disorder). Breech presentation (? neuromuscular disorder).

Examination

This should bedetailedwithcareful physical abnormalities. 0

examination of any

Describe abnormal signs accurately. Obtain photographic records if possible. Are the malformations present part of a recognized syndrome (e.g. Downs syndrome) or sequence (e.g. PierreRobin sequence)?

If immediate recognition is not possible, identifysome welldefined unusual physical signs as 'handles' (e.g. ptosis, microcephaly, polydactyly, short limbs, hypogenitalia) and use the handle or a combination of them to scrollthrough the possible

70 CONGENITAL MALFORMATIONS AND BIRTH DEFECTS

diagnoses. This process may be facilitated by the use of computerized databases.

Investigations

Chromosome analysis. Specialized genetic techniques (e.g. DNA probes for Di George or Williams’ syndromes). Cytogenetic analysis of specific tissue samples (e.g. skin fibroblast culture for the diagnosis of 12p tetrasomy Killian-Pallister syndrome). Skeletal X-rays (e.g. osteogenesis imperfecta congenita). Ultrasound imaging (e.g. of head or abdomen). Haematological (e.g. TAR syndrome). Biochemical analysis (e.g. amino-aciduria, renal tubular acidosis in Lowe syndrome).

Management

Depending on the malformations/deformations present, specialist teams may be required, e.g. ophthalmologist for ocular defects, ENT surgeon for ear and nose defects, maxillofacial and plastic surgeons for facial anomalies (e.g. cleft lip and palate), orthopaedic surgeons and physiotherapists for limb malformations and deformations. If the diagnosis remains uncertain always seek review by a clinical geneticist. Genetic counselling is vital in most cases (recurrence risks and possible future antenatal diagnosis). Infants with feeding difficulties may require inputfrom dieticians, speech and language therapists and the assistance of community nurses. Neurodevelopmental follow-up will be required. Where appropriate, put the parents in touch with theappropriate parents’ self-help organizations (e.g. Association for Spina Bifida and Hydrocephalus).

e

e

e e

Further reading Baraister M, Winter RM. Colour Atlas of CongenitalMalformationSyndmmes. London: Mosby-Wolfe, 1996. Jones KL. Smith’s Recognizable Patterns of Human Malformation, 5th edn. Philadelphia: W.R. Saunders, 1997. Wiedemann H-R, Kunze J. Clinical Syndromes, 3rd edn. London: Mosby-Wolfe, 1997.

Related topics of interest Chromosomal abnormalities (p. 49) Neural tube defects (p. 203)

CONGENITAL MALFORMATIONS AND BIRTH DEFECTS 71

The care of a dead or dying baby and hislher family has been called the neglected side of neonatal care. It is a daunting task that must be carried out sensitively and empathetically. Most parents need alot of time to deal with the issues, and on a busy neonatalunit, staff must be careful not to rush them. In major neonatal units, 5 1 0 % of all admissions die, including approximately 20% of thosein intensive care. Common causes of death include extreme prematurity, lethal anatomical and biochemical abnormalities and birth asphyxia. In some, death will be completely unexpected: the parents may have never even contemplated it.For others, the congenital abnormality may have been diagnosed before birth, or the parents may have witnessed a heroic fight to save their very preterm baby against all odds. If time permits it is best to ask the parents if they want any religious blessing or naming of their baby when the critical nature of theillness is recognized, rather than waitinguntil death is imminent. It is also the time to take a firstset of photographs. Whatever the circumstances, most parents instinctively feel that their baby should not die ‘alone’ in a mass oftubes and wires. They wantto cuddle their dying baby, even though they may be very afraid of this at first. In some circumstances. continuation of intensive care is to prolong death notto sustain life. Staff must therefore help parents recognize that nothing more can be doneto save their baby. Parents then usually accept discontinuationof intensive care so long as full nursing care continues while they holdtheir baby and say goodbye. It is unethical to let the baby suffer in any way during this period - and parents are both acutely and persistently upset if their baby is distressed. It is a period of intensive nursing care - and doctors must be involved! The baby should be dressed in clothes of the parents’ choice and taken to them in a quiet and entirely private room. Atthis point the baby is usually still alive. Whiletheparents are holding their baby,theyshouldbeasked if theywish to have photographs taken of the threeof them together. Skilled carers can often point outsome beautiful features of the baby - the hair, ears, face and hands - to help parents really look at and remember their baby whose face may have previously been hidden behindventilator apparatus. Even very dysmorphic babies have fine features for parents to remember - wriggly toes and long fingers, perhaps! The moment of death - when the heart stops - cannot be recognized by parentsas the baby quietly passes awayafter a period of apnoea. The heart may beat for 20-30min after the final breath. Parents are comforted to be told that death will not be a cataclysm, but a quiet fading of life while their baby is unconscious and unaware of the change. After the death the parents may wishto be alone with their baby. If so, they must be given as much time as they desire - sometimes several hours. They should have free access to a phone to contact relatives, and the extended family shouldbe allowed to gather with the baby and parents if that is what they wish. Staff should pop in and out from time to time to ensure that they are coping and to offer support if needed. When they are ready to leave, they must go to an environment where on-going supportis available. This may be a special bereavement suite on the postnatal ward where neonatal staff and midwife counsellors can help,or it may be home with the support of grandparents, relatives and other health professionals. The parents should know where their baby is going next, and should be advised that they can see h i d e r again at any time. For the staff there are practical things to doand achieve. A most useful checklist published

72 DEATH OF A BABY

by the Royal College of Obstetricians and Gynaecologists is used in many units. A modified list of tasks (some of which have been covered above) based on that checklist includes: Mother and father informed of death. Parents given opportunity to handle baby. Consultant paediatrician and consultant obstetrician informed. General practitioner informed. Community midwives and/or healthvisitor informed. Consent for post-mortem (PM) requested - givedrefused. Parents offered ‘Guide to the Post-Mortem Examination’. PM form completed:date and time of PM confirmed. Preliminary results of PM explained to parents. DeatWstillbirth certificate completed and given to parents. Information about funeral arrangements givento parents. Parents offered booklet ‘Saying Goodbyeto Your Baby’. Parents told about supportgroups and given contact telephone numbers. Parents seen by counsellor/social worker. Parents seen by consultantobstetricidpaediatrician. Religious adviser notifiedif parents wish. Religious service requestedlamanged. Photographs taken of baby- with parents if wished. Footprintsthandprints of baby taken. Other keepsakes collected: parents advised ofbook of remembrance. Follow-up visits arranged. Some of the items on this list must be dealt with promptly - the family doctor and community midwife must know of the death before grieving relatives call them. If religious beliefs allow, discussion about the PM and funeral may be left to the following day, when the parents will be more able to absorb what is said to them. Follow-up meetings must be arranged, The paediatrician should have clear goals for such visits. At a first meeting the tasks of the paediatrician include:

e

Reviewing the baby’s medical problems and answering all questions about them. Discussing the findings of the PM ifone was performed. Ensuring that appropriate postnatal follow-upis in place, including an appointment with a consultant obstetrician if necessary. Assessing how the couple are grieving. Can they talk to eachother about the baby, using hidher first name? Have they had a funeral and said goodbye? Are they grieving differently - is the father buried in work while the mother weeps at home? Are they eating and sleeping reasonably under the circumstances? Reminding them of support groups and encouraging contact if appropriate. Helping them to begin to look to the future. Considering if genetic counsellingis needed. Asking if the parentsare thinking about the next pregnancy. Could therebe an unplanned early conception - would this be a problem if it happened? Explaining the risks of the same thing happening again.

DEATH OF A BABY 73

0

Counselling the parents that it is normal to feel sad for many months after such a loss, but that they should seek help if symptoms worsen or persist too long.

It is virtually impossible to achieve all this at one visit soon after the death. The paediatrician or a counsellormay need sessions with the parents over a period of several months, and these may be best held away from the hospital. Last but not leastis the question of caring forthe carers.Junior nurses and doctors find perinatal deaths extremely distressing and must be given time to reflect on the issuessurrounding an individual death, particularly if they feel guilt as partof their grief. Senior colleagues must support and counsel them. These same senior staff who may have been involved in very distressing conversations and procedures must learn totum to each other forhelp, or be confident of strong support outside the neonatal unit. The stress of dealing with a neonatal death is one of the experiences known to contribute to psychological 'bum-out' of neonatologists.Its impact should not be dismissed lightly. The Stillbirth and Neonatal Death Society can be contacted at: Stillbirth and Neonatal Death Society 28 Portland Place London W 1 N 4DE Tel: 0171 436 5881 (Helpline) 0171 436 7940 (Administration)

Further reading Guide to the Post-Mortem Examination. London: Department of Health, 1994. McIntosh N. Eldridge C. Neonatal death - the neglected side of neonatal care? Adlives of Disease in Childhood, 1984; 59: 585-7. Royal College of Paediatricsand Child Health. Withholding or Withdrawing Life Saving Treatment in Children. Royal College of Paediatrics and Child Health, 1997. Royal College of Obstetricians and Gynaecologists. Repon of theWorkingPart?, on Management of Perinatal Deaths. London: Royal College of Obstetricians and Gynaecologists, 1985. Saying Goodbye to Your Baby. London: Stillbirth and Neonatal Death Society, 1997. Wigglesworth JS. Perinatal Pathology.2nd edn. London: W.B. Saunders, 1996.

Related topicsof interest Congenital malformations and birth defects (p. 70) Extreme prematurity (p. 80) Hypoxic-ischaemic encephalopathy (p. 128) Inherited metabolic disease - investigation and management (p. 156)

74 DEATH OF A BABY

There are three main groups ofinfants to consider. 1. The otherwise well term or near-term newborn infant following a hospital delivery. 2. Term or near-term infants with proven or suspected disorders, e.g. congenital anomaly, which require medical intervention(s) in theperinatal period. 3. Preterm infants who have required varying periods of care on the neonatal unit.

The wellterm or neartermnewhorninfant

There is no consensus on theoptimumpost-partumlengthof stay for healthyterm infants. Thereis aworldwide variation in policiesandguidelinesonthe perinatal stay.Generally,the usualstay for avaginaldelivery in most countries is 1-3 days and up to 7 days after a Caesarean section. Discharges may, however, be done as early as 6-8 hours depending on, among other things, social and financial factors. The timing of each discharge is probably best individualized for each infant dependingontheindividualmedical, social andeconomic aspects. Prior to discharge, however, the following important points should be noted: 0

0

0

The infant is feeding well. The infant has voided urine and passed stools. The physicalexamination is normal. There is no evidenceof clinical jaundice in thefirst 24 hours. The mother is well and capable of looking after her newborn infant(s). There are no adverse social, environmental or familial factors which would jeopardize the safety or wellbeing of the infantfollowingdischarge(e.g. history ofdomesticviolence, child abuse or homelessness). Anynecessaryvaccinations(e.g. for hepatitis B or BCG have been administered).

The problematicterm or near-terminfant

These infants may be dischargedonce their problemshave resolved(e.g. transient tachypnoea) or onceappropriateinvestigations or therapieshavebeen instituted (e.g.renalscan for antenatallydiagnosedhydronephrosis)andfollow-up appointment(s) have been made.

The ex-preterminfant

The discharge of infants whohaverequiredneonatal carefor prematurityand related disordersrequiresmoreplanning. Once it looks likely that the infant’s discharge is imminent, the parent(s) should be notified so they can prepare themselvesfor their baby’s homecoming. This enables the parentsto receive a comprehensive training whichreducesparentalanxietyand increases their satisfaction. The following shouldbe addressed.

DISCHARGE PLANNING AND FOLLOW-UP 75

I . Social and environmentalfactors e

e e

Assess adequacy ofhome environment and domestic arrangements and obtain a home visit by the health visitor if necessary. If home oxygen therapy will be required, make arrangements for the appropriate equipment to be installed. Check that thereare no concerns regarding child protection matters (e.g. parentaldrug oralcohol abuse, maternal postnatal depression or other adverse factors) whichwould prejudice the infant's care.

2. Parental factors e Instruct parents on the special requirements of their infant (e.g. general routine infant care after discharge, positioning, avoidance of over-heating, risk of cot death, avoid smoking indoors especially with home oxygen therapy). e Inform parents of the commonsigns of ill-health and when to obtain assistance for their infant. e Assess adequacy of parenting skills andteach parents where appropriate (e.g. cardiopulmonary resuscitation training for infants onsupplemental oxygen therapy). e The mother should be invited to 'room in' on the neonatal unit to familiarize herself with her infant's care requirements (especially first-timemothers) and this also gives the NICUstaff an opportunity to assess parental skills and competency. 3. Infant factors 0 Temperature should be maintained in an open cot. e The infant should be feeding well with a steady weight gain (10-30 g/day). e There should be no recent apnoeas or bradycardias ( 5 - 8 days before discharge). e Infants at risk of retinopathy of prematurity (ROP) should have been screened for this and any outstanding follow-up appointments formalized. e High-risk infants (e.g. severe jaundice, neonatal meningitis, congenital rubella or cytomegalovirus (CMV). family history of deafness) should have a formal audiological examination. e No absolute discharge weight requirements exist, though most infants are >l800 g at discharge and >35-37 weeks gestation.Infants of birthweight 37 weeks gestation) dueto associated problems of prematurity. e Earlier home discharges are possible in the presence of comprehensive support in thecommunity by dedicated and skilled neonatal nurses and competent parents who have been adequately prepared prior to discharge.

76 DISCHARGE PLANNING AND FOLLOW-UP

4. On discharge honle Ascertain that the parentsare clearon how to administer any necessary medications and how to obtain further supplies. Documentanyimmunizationsgivenin the parent-held record. Givewrittenrecordsofanyfollow-upappointments or hospital visits. Send summary of hospital course, medications and followup plans to the general practitioner and any other relevant primary care workers(e.g.health visitor, community midwife) with copies to the relevant hospital records.

Who needs follow-up?

Conditions needing follow-up are numerous and partly depend on the available resources andexpertise. While a complete list would be inappropriate for every setting, some of the common reasons include:

e

Prolonged jaundice. Infants at risk from child abuse. Infants of drug abusing mothers. Congenital infections (e.g. CMV). Haematological disorders (e.g. thalassaemia). Infants who had severe sepsis (e.g. meningitis). Complications of neonatal intensive care (e.g. BPD, IVH, ROP). Infants withmetabolicorendocrinedisorders (e.g. suspected hypothyroidism). Congenital malformations and birth defects (e.g. renal and urinary tract disorders). Infants who experienced significant perinatal complications (e.g. birth injuries, asphyxia).

Further reading Britton JR (ed). Early perinatal hospital discharge: issues and concerns. Clinics in Perinatology, 1998; 25 (2). Powell PJ, Povell CV, Hollis S, Robinson MJ et al. When will my baby go home? Archives of Disease in Childhood, 1992; 67: 1214-6. Casiro OG, McKenzie ME, McFadyen L et al. Early discharge with community-based intervention for low birthweight infants: a randomized trial. Pediatrics, 1993; 92: 128-34. Rawlings J. Scott J. Post-conceptional age of surviving low birthweight preterm infants at hospital discharge. Achives of Pediatrics and Adolescent Medicine,1996; 150: 260-2. Samuels MP, Southall DP. Home oxygen therapy. In: David TJ (ed). RecentAdvances in Paediatrics, No. 14. Edinburgh: Churchill Livingstone, 1995; 37-51.

Related topics of interest Bronchopulmonary dysplasia (p. 38) Home oxygen therapy (p. 118)

Postnatal examination (p. 244) Retinopathy of prematurity (p. 287)

DISCHARGE PLANNING AND FOLLOW-UP 77

EXTRACORPOREAL MEMBRANE OXYGENATION ECMO is a technique for treating severe respiratory failure from which the patient can be expected to recover within 1-2 weeks. One of its main applications is the treatment of term babies with meconium aspiration syndrome, CDH, PPHN or pneumonia. Contraindications to ECMO include major congenital abnormalities, IVH, irreversible cardiopulmonary disease, NEC and a period of asystole. Before starting ECMO, each baby should have echocardiography to exclude cyanotic CHD (particularly total anomalous pulmonary venous drainage) and an ultrasound scan of the brain. Prolonged high-pressure ventilation causes lung damage, so babies need to be transferred onto ECMO ideally after less than 7 to 10 days' conventional ventilation. It is used only in babies 235 weeks as the heparinization could cause severe intracranial haemorrhage in more immature infants. The jugular vein is cannulated and blood flows into a primed heparinized circuit with a pump, membrane oxygenator and bubble trap before being returned to the baby, either via the carotid artery (veno-arterial ECMO) or right atrium (veno-venous ECMO). The latter is now the treatment of choice asit avoids the need totie off the cannulated carotid artery andthence relying on anastomoses to maintain the circulation from the contralateral carotid artery. During trcatment the baby is gently ventilated to maintain lung inflation, but the main source of gas exchange is the membrane oxygenator. Following promising reports of trials on small numbers of babies, over 75 ECMO centres opened in the US and submitted data tothe ECMO Registry. Currently, over 12000 infants have been treated, with an overall 80% survival, but 95% survivalfor meconium aspirationsyndrome. These infants would have had expected mortality rates of approximately 80%. In the UK. a more circumspect approach was taken as fewer term babies were seen with respiratory failure. In a multicentre, randomized trial of 185 term babies, 30 of 93 babies allocated to ECMO died, compared with 55 ofthe 92 allocated to conventional management (CM). The relative risk was 0.55 (95% CI, 0.39-0.77), equivalent to one extra survivor for every three to four babies allocated ECMO. However. outcome in those with diaphragmatic hernia was poor: all 17 in the CM group died, as did 14 of the 18 allocated ECMO. Moredata are needed tohelp understand the role of ECMO in infants with diaphragmatic herniae. When that group was excluded, the survival was 79% in the ECMO group, 5 1% in those allocated CM. Of the 124 initially followed to 1 year, 51% of those allocated to ECMO were alive with no signs of impairment (74% of survivors), compared with only 28% of those allocated CM (71% of survivors). ECMO therefore has a clearly established role in the treatment of term babies with severe respiratory failure. Technical problems of cannulation make it difficult to use this technique in smaller babies. The development of tubing with heparin bonded onto the walls may enable a reduction in systemic heparinization. Treatment with inhaled NO in babies who would normally qualifyfor ECMO reduces the need for ECMOby about 60%.Pleasing as this is, it does mean that neonatal transport incubators will need NO circuits in the future to transfer babies who have become NO-dependent but still need to be transported to an ECMO centre. There remains the question as to thethreshold for startingECMO in babies with meconium aspiration, pneumonia or PPHN (persistent fetal circulation), and indeed diaphragmatic hernia. The criterion that is usually considered is the oxygenation index (01) which is calculated as:

78 EXTRACORPOREAL MEMBRANE OXYGENATION

Mean airway pressure (cmH,O) X FiO, (%) + post-ductal PaO, (mmHg). In the UK trial, the entry criterion was an 01of 240, or a PaC02 of >12Wa for 3 hours. In view of the success of ECMO it may be best to lower the threshold to an 01of 30 or even 25, though there are no published data to support this. The UK trial clearly showed, however, that referral of very ill infants to ECMO centres resulted in some infants dying before ECMO could be instituted. The collaborative UK ECMO trial l-year follow-up data show that ECMO support reduces the risk of mortality, without a major concomitant rise in severe disability, by about 45%, regardless of the severity of the infant’s condition. The resultsof the economic evaluation, carried out alongside the trial, basedon the principalend-point of death or severe disability at age l year, found the additional cost of ECMO per additional survivor to be within the range of other life-extending technologies such as renal transplantation.

Further reading Graziani W, Gringlas M, Baumgart S. Cerebrovascular complications and neurodevelopmental sequelae of neonatal ECMO. Clinics in Perinatology, 1997; 24 655-75. Kanto WP, Bunyapen C. Extracorporeal membrane oxygenation: controversies in selection of patients and management. Clinics in Perinatology, 1998; 25: 123-35. Sol1 R E Neonatal extracorporeal membrane oxygenation - a bridging technique. Lancet, 1996; 348: 70-1. UK Collaborative ECMO Trial Group. UK collaborative randomized trial of neonatal extracorporeal membrane oxygenation. Lancet, 1996; 348: 75-82. UK Collaborative ECMO Group. The Collaborative UK ECMO Trial: follow-up to 1 year of age. Pediatrics. 1998; lOl(4).

Related topics of interest Congenital diaphragmatic hernia (p. 57) Meconium aspiration syndrome (p. 189) Persistent pulmonary hypertension of the newborn (p. 237)

EXTRACORPOREAL MEMBRANE OXYGENATION 79

The last 30 years have witnessed remarkable improvements in the survival of small preterm infants. US data, for instance, shows a 70-fold increase in the number of survivors per lo00 live births between 1960 and 1983. The introduction of surfactant in the last 10 years has produced even further improvements in survival (but with no concomitant reduction in neurodevelopmental morbidity), particularly in the lowest birthweights where survival had previously been exceptionally low. Until recent years, 28 weeks was considered the edge of viability for aneonate.However, this ‘edge’hasbeen retreating to thecurrentlyperceived limit of extrauterine survival (22-23 weeks). Intact survival of a 280g infant has been reported. The term extreme prematurity is now used in everyday parlance to refer to gestations at the lower margin of viability, particularly those of 22-25 weeks (and not the strict definition of R 8 weeks). 0

0 0

Extremely preterm babies make heavy demands on health resources. They have a high mortality rate and a high risk of neurological or respiratory morbidity should they survive. Gestational age is a better predictor of neonatal mortality than birthweight. The greatconcern felt for individualbabiesand for the group as awholehasled to careful analysis of outcomes. The hope is that such information will enable appropriate decision-making that will in turn improve survival and the quality of survival.

Survival

0

Manyvaluable data are emergingfromthe UK EPICure studywhichwasapopulation-basedstudyontheoutcomes for babiesborn at 20-25 weeksgestationinthe UK and Ireland during 9 months in 1995. 803 of 3781 such babieswereadmitted to NNUs. Data were available on94%of the admissions.

Table I summarizes some outcomes at the expected date of delivery (EDD) of the babies. Survival and neurological data will be collected again after a further 2 years. The table also shows data collatedbyRennieofreports on survivalfrom 1977 to 1993, although the collectionof denominator data (i.e. the total number of babies born at a given gestation) probably varied between reports.

Table 1. Survival by gestation Gestation (weeks)

Admission rates to N W

Survival (%) to EDD of those admitted to NNU

Survival (%) as reported by Rennie with 95%C1

28

16 (12-19) 35 (31-38)

(%l 23 24 25 26

50

61

35 54

80 EXTREMEPREMATURITY

48 (45-50) 57 (55-60)

Neurodevelopmental disability and handicap

The issue is not just of survival butof intact survival. By the time of their EDD: 50% of survivors in the EPICure study werestill in oxygen. 17% had parenchymal cysts andor hydrocephalus on their last scan. 13% had needed treatment for retinopathy of prematurity.

Normality has proved hard to define: initial studies concentrated upon major handicaps - cerebral palsy, deafness, blindness and major learning difficulties. It is now recognized that subtle effects upon behaviour with reduced attention span and increased distractibility contribute to learning difficulties and school failure insomeex-prematurebabies.Manyofthese children need extra help to fulfil their potential. The incidence ofchroniclungdiseasevariesinverselywithgestationand adds tothe morbidity of the most preterm babies. Table 2 shows some published data onhandicap rates amongst survivors of extreme prematurity. Rates vary between centresbecauseoutcomesmaygenuinelybe different, or because definitions and the age of assessment vary. Furthermore, the 95% confidence intervals for these proportions of handicapped children are very wide - in excess of 20% at the lowest gestations, where the numbers of survivors are small. Nevertheless, about 25% of surviving babies of26 weeks gestation have severe disability: most centres have higherrates of handicap below 26 weeks.

Management at birth

0

0

0

Twoexperiencedpaediatriciansshouldattendthe birth of an extremely preterm baby. If time allows, they should see the parents beforehand, discuss the possible outcomes and draft a plan of management. However, it may be very difficult to communicate effectively with a distressed couple or mother once preterm labour has started. hior to birth, the chances of normal andor handicapped survival should be assessed and discussed. The purpose of

Table 2. Disability by gestation in survivors Severe disability survivors in Gestation Handicapped Severe disability (weeks) survivors (%) at 4 years (a) at 1 year (%) Data from Rennie’s Babies born 1984- 6 Babies born 1983 -94 Data from Northern region review”: Data from Oxford region 23 24 25 26

50 (I25 weeks)

31 21

24 (I25 weeks) (26

27

and 27 weeks)

’Rennie’s review included the Oxford data. EXTREME PREMATURITY 81

resuscitation and neonatal intensive care is to achieve a healthy outcome, but this goalis not always reached. Doctors need to be realistic and help parents accept the very realdifficulties. This isparticularlyhardfor those who have waited many years and perhaps had multiple courses of infertility treatment. Individual units and paediatricians reach their own ethical decisions. Inthelightof published survivaland morbidity rates, few paediatricians encourage active resuscitation below 23 weeks. At 25 weeks andabove, full resuscitation and intensive care should be started, remembering that to start intensive care is not to continue it unconditionally. If the likelihood of severe neurological handicap becomes very high, there is the option of discontinuing intensive care and offering palliative nursing care. The greatest dilemmas lie at 23 and 24 weeks.A personal approach is to discussthe issues jointly with parents andobstetricians, and tooffer resuscitationandthenearly assessment - with a view to stopping or continuing intensive care. If riskfactorssuch as prolonged oligohydramnios or reversed EDF in the fetus havebeen recognized andthe chances of viability are loweredevenfurther,thenresuscitationmaybe reasonably withheld if allagree.When circumstances do not permit a full discussion and assessment before birth, resuscitation is the rule. The baby could be several weeks older than the mother thinks!

Special notes

The 3-year survival for infants of birthweight GOOg is extremely poor (3.4%). In infants of birthweight SOOg, 90% of all deaths occur within the first 3 days of life. World literaturereportsveryfew survivors at22weeks (mostly from Japan, but none were free of neurological sequelae). Some degree of impairment is found in up to 70% of survivors at 23 weeks gestation. Female infantshave a survival advantage equivalent to almost one additional gestational week. In extremely preterm infants, morbidity is inversely related to birthweight and gestational age.

Further reading Bregman J. Developmental outcome in very low birthweight infants: current status and future trends. Pediatric Clinics of North America,1998; 45: 673-90. Johnson A,Townshend P, Yudkin P, Bull D, Wilkinson AR. Functional abilities at age 4 years of children born before 29 weeks of gestation. British Medical Journal, 1993; 306: 1715-8.

82 EXTREMEPREMATURITY

Rennie JM. Perinatal management at the lower margin of viability. Archives of Disease in Childhood, 1996; 74: F214-8. RoyalCollege of PaediatricsandChildHealth. Withholding or WithdrawingLife-saving Treatment in Children. London: Royal College of Paediatrics and Child Health, 1997. Tin W, Wariyar U, Hey N (Northern Neonatal Network). Changing prognosis for babies of less than 28 weeks gestation in the north of England between 1983 and 1994. British Medical Journal, 1997; 314: 107-1 1 Wilkinson AR, EPICure Study Steering Group. The extremely pretenn baby - a populationbased study of outcomes of babies born before 26 weeks gestation in the UK and Ireland. Pediatric Research, 1997; 42: 402 (Abs. 103).

Related topics of interest Bronchopulmonary dysplasia (p. 38) Death of a baby (p. 72) Multiple pregnancy (p. 192) Pregnancy complications and fetal health (p. 247) Resuscitation (p. 282)

EXTREME PREMATURITY 83

FEEDING DIFFICULTIES Feeding difficulties are extremely common in the newborn period.These may be categorized a.. transient or persistent. Transient feeding difficulties invariably are related to perinatal factors and commonly resolve within thefirst few days or weeks of life. Persistent feeding difficulties suggest an underlying organic cause and require careful evaluation to determine the c o m t aetiology and therefore appropriate management. For transient feeding difficulties, both maternal and infant factors can be identified.

Transient feeding difficulties Maternal factors

0 0

Infant factors

Inexperienced first-time mothees). Pregnancy-related maternal illness (e.g. severe preeclampsia,eclampsia,deliverycomplications,postnatal depression). he-existing chronicmaternal illness (e.g.rheumatoid arthritis, multiple sclerosis). Breast abnormalities in breast-feeding mothers (e.g. inverted nipples, previousbreast surgery or injury). Maternalmedication - drugs takenduringpregnancy andor delivery may adverselyaffect the infant, e.g. benzodiazepines (drowsy infant) and methadone (neonatal drug withdrawal syndrome). Maternal anxiety. hematurity (immature suck and swallow reflex). Traumaticdelivery(instrumentaldeliverywith injury). Hypoglycaemia. Birth asphyxia. Cold stress. Intrauterine growth restriction (TUGR). Sepsis.

facial

With appropriate support from the midwifery and neonatal staff, most mothers and their infants can be successfully supportedthroughthe initial transitional period to feed their infantsby their preferredmethod. If feeding is particularly poor, capillary bloodsugarsshould be monitoredregularly (until they are persistently 2 4 mmolA). Nasogastric tube feeds may be required in the preterm, small for gestational age, or large infants of diabetic mothers.

Persistent feeding difficulties A carefulsearchoftenrevealsa numerous.

84 FEEDING DIFFICULTIES

cause in mostofthese

infants. The possiblecauses are

Local(e.g. facial nervepalsy,bulbarandsuprabulbar palsy, vocal cord palsy). Central (e.g. CNS malformations, severe intracranial haemorrhage, severe hydrocephalus, seizures).

Neurological abnormalities

Neuromusculardisorders 0 0

0

Syndromic disorders

0 0 0 0

0

Anatomical defects

0 0 0 0

0 0 0 0 0

Metabolic disorders

0

0 0

Spinal muscular atrophy. Myotonic dystrophy and other muscular dystrophies. Prader-Willi syndrome. Myasthenia gravis. Down’s syndrome. Moebias syndrome. Pierre-Robin sequence. Roberts’ syndrome. Beckwith-Wledemann syndrome. Cleft lip and palate. Submucous cleft. Choana1 atresialstenosis. Oesophageal atresia (associated polyhydramnios). Tracheoesophageal fistula. Laryngeal webs and clefts. Oesophageal compression (e.g. vascular rings). Gut malrotation. Oropharyngealvascularmalformations(e.g.carvenous haemangioma). Tumours. Galactosaemia. Hypothyroidism. Organic and amino acidopathies (e.g. propionic acidaemia, non-ketotic hyperglycinaemia). Urea cycle defects. Other inherited metabolic disorders.

Miscellaneous disorders

Isolated swallowing disorders with pharyngeal and cricopharyngeal incoordination. Chalasia or achalasia of oesophagus. Stomatitis. Oesophagitis.

Investigations

pH monitoring (reflux oesophagitis). Endoscopy (reflux oesophagitis). Barium swallow and follow through(haitus hernia, malrotation). Chromosomes (dysmorphic infants). Laryngoscopy. Video fluoroscopy. Cranial ultrasound. Cranial CT/MRI.

FEEDING DIFFICULTIES 85

Management 0

0

0

0

Oropharyngealstimulation(non-nutritivesucking). Use of special teats and bottle (cleft lip/palate). Orthodonticdevices (cleft lip/palate). Nasogastric tube feeding. Gastrostomy (persistent difficulties especially in the neurologically impaired). Nissenfundoplication(especiallyinneurologicallyimpaired infants).

Multidisciplinaryteams are often required in managing these infants. Infants with anatomical defects (e.g.cleft lip and palate, oesophageal atresia) may require the input of plastic surgeons, orthodontists. faciomaxillary surgeons, speech therapists and dietitians. Even in the absenceof anatomical defects requiringsurgery,speechandlanguage therapists and dietitians are often required to optimize the calorie intake of such infants. Similarly, a paediatric neurologist and clinical geneticist may offer valuable advice in infants with suspected neurological disorders and dysmorphic features, respectively. Remember to exclude feed intolerance, especially with a family history of atopy, cow's milk protein intolerance, or other rarer metabolic disorders.

Further reading Arvedson JC, Rrodsky L. Paediatric Swallowing and Feeding Assessment and Management. London: Wham Publishers. 1993. Cooper PJ, Stein A (eds). Feeding Problems and Eating Disorders in Children and Adolescence. Reading: Hanvood Academic Publishers, 1992. Gisel EG, Birnbaum R, Schwartz S. Helping the feeding impaired child. In: David TJ (ed). Recenr Advances in Paediatrics,Number 16. Edinburgh:ChurchillLivingstone,1997; 59-7 1. Hyman P. Gastroesophageal reflux: one reason why baby won't eat. Journal of Pediatrics, 1994: 125: S103-9.

Related topicsof interest Congenital malformations and birth defects (p. 70) Hypoxic-ischaemic encephalopathy (p. 128) Nutrition (p. 221)

86 FEEDING DIFFICULTIES

The management of fluid and electrolyte administration is vital in the management of sick newborn infants. The handling of water and solute by the immature kidneys is impaired and this is often compounded by large water losses through the highly permeable immature skin. To maintain normal fluid andelectrolyte balance it is therefore necessary to accurately control their administration.

Water balance

Approximately 75% of the total bodyweight is water, half of which is extracellular fluid. A reduction of the extracellular space occurs during the first weekof life, accounting for most of the 10-15% reduction in bodyweight; inadequate calorie intake accounts for the remainder of the weightloss. Respiratory distress syndrome (RDS) is associated with a delayed contraction of the extracellular fluid volume which occurs with resolution of RDS.

Factors associated with increased water loss

e e e e e e

e

Factors associated with water overload

e e

Remedial steps to maintain optimal water balance

e e e

Adverse effects of fluid overload

e e

Electrolyte balance

Use of radiant warmers. Phototherapy. Preterm thin skin. Poor humidification of respiratory gases. Watery stools. High ileostomy losses. Osmotic diuresis (e.g. glycosuria). Low ambient humidity. Excess fluid administration. Inappropriate sodium administration. Conditions associated with inappropriate antidiuretic hormone (ADH) secretion (e.g. pneumonia, RDS). Avoid nursing very preterminfants under radiant warmers. Cover infants with plastic sheeting to reduce fluid losses. Nurse newborn infants in humid environment. Humidify respiratory gases adequately for infants receiving respiratory support. Persistence of ductus arteriosus. Chronic lung disease. Increased mortality.

The main extracellular and intracellular cations are sodium and potassium, respectively. Sodium absorption is under the influence of renin-angiotensin-aldosterone, while potassium absorption is influencedbymineralocorticoidswithpotassium being exchanged for hydrogen in the kidneys. Potassium excretion is greatly reduced in renal failure. Sodium supplementation is not required until after the reduction of extracellular fluid space (24-48 hours), but thereafter sodium may be

FLUID AND ELECTROLYTE THERAPY 87

supplemented at 4 mmoVkg/day (or more depending on serum sodium) in preterm infants and 2 mmolkg/day in term infants. Aim to keep sodium between 135-140 mmoyl. Potassium is supplemented at 2 mmol/kg/day if urine output is satisfactory. While calcium is predominantly stored in bone, 40% of that in the extracellular fluid is bound to albumin, the rest (approximately 1.25 mmolA) being free ionized calcium (ionized calcium falls with rising pH). For every 10g fall in albumin below 40g/l, the total calcium is reduced by 0.05 mmoyl. Calcium homeostasis is under the influence of calcitonin, parathormoneandvitaminD(1.25-dihydroxyvitaminD). Parathormoneincreasescalciumabsorptionfromthegut andkidneys.Intravenoussupplementationshouldprovide 2 mmolkg/day and oral supplementation 1.75-3.5 mmoVkg/day (with a calcium phosphate ratio of 1.4-2:l). Avoid rapid i.v. administration of calcium (as calcium gluconate)as this causes bradycardia, and beware of extravasation (produces unsightly scars). Phosphate, like calcium, is a major constituent of bone and its absorption from the gut and kidneys is influenced by vitamin D and parathormone. Intravenous supplements of l mmoY kg/day are appropriate with oral supplements of 1.6 mmol per 100 kilocalories. Human milk contains low phosphorus levels (0.4mmolA),making it mandatory to supplementpreterm infants fed on breast milk. Magnesium is mainly an intracellular ion excreted by kidneys and absorbed from the gut. Always check serum magnesium when hypocalcaemia is present. For urgent replacement, giveaslowinfusion of 25%magnesiumsulphate at 0.5 mmolkg or intramuscularly as 0.1 mlkg of 50% magnesium sulphate. For oral supplementation. give as 10% magnesium chloride once daily. Diuretics may cause hypomagnesaemia. Chloride is an extracellular ionwhoserequirements are usually met from the normal dietarychloride.

Monitoring fluidand electrolyte therapy

Changes in weight relate well to total body water in newborns. Daily weights are a valuable aid in fluid management. Similarly,urineoutputshouldbemonitored(minimum 1 ml/kg/ hour and maximum7 mlkghour). 0

0

0

Measureserumsodium,potassium,urea,creatinineand calcium daily in sick infants. Withabnormal electrolytes andor largefluidrequirements, 6-hourly electrolyte determinations may be required. Paired measurements of plasma and urine osmolarity are helpful in diagnosing inappropriate ADH secretion.

88 FLUID AND ELECTROLYTE THERAPY

Plasmaosmolarity = (2 X sodium) + (2 X potassium) glucose + urea (all values in mmoVI).

+

Suspect inappropriate ADH if the urine is not maximally dilute (>l00 mosmolfl) with serum osmolarity of 90% of cases. Ninety-nine percent of terminfants pass meconium within 48 hours of birth. Bilious vomiting, marked abdominal distension and complete intestinal obstruction. Chronic constipation following normal passage of meconium. Rectal examination shows normal anal tone and is followed by explosive foul-smellingstools and gas. Meconium plug syndrome: 10-208 of infants with this disorder may have Hirschsprung’sdisease. Enterocolitis(which is mostcommon in thefirst 2-4 weeksof life). Thisis themain cause ofmortalityin Hirschsprung’s disease and is a consequence of delayed diagnosis. Inability to pass stools leads to massive abdominal distension, increased intraluminal pressure, decreased intestinal blood flow and a breachof the mucosal integrity. The stasis also encourages bacterial proliferation (Clostridium dificile, anaerobes.coliforms)and sepsis. The infant presents with profuse mucusy and bloody diarrhoea,abdominaldistension.biliousvomiting,hypotension (large fluidlosses)andoccasionallyshock.Left untreated, 33% of infants withHirschsprung’sdisease develop enterocolitis within the first3 months of life and a third of these develop it within 30 days of birth. Once an infant hasdeveloped enterocolitis he/sheremains at increased risk of further bouts of enterocolitis, even after a successful pull-through procedure.

1. Radiology. Plainabdominalfilmsshowgas-filledbowel loops throughout the abdomen except for the pelvis which is devoid of gas. A barium contrast enemain a previously unprepared colon shows a small calibre aganglionic segment followed by a funnel-shaped ‘cone’ or ‘transitional zone’ leading into a normal but dilated proximal colon. However, a barium enema is less accurate in the neonatal period than at any other time, as a transitional zone may not be seen before the age of 2 weeks and a megacolon may not be present. Delayed films (after 24 hours) show retention of contrast material. A barium enemamay,however,reveal other disorderswhich cause neonatal lower bowel obstruction.

2. Manometry. Failure of the internal analsphincter to exhibit a relaxation wave in response to inflation of a balloon inserted into the rectumis diagnostic of Hirschsprung’s disease (>W%accuracy) butit cannot be performedin infants of c3kg in weight (39 weeks post-conceptualage) asthe anal relaxation reflex may be physiologically absent. Diagnosis of ultrashort-

HIRSCHSPRUNG’S DISEASE 111

segmentHirschsprung’sdiseasecanonly be madewith manometry which shows failure of the internal sphincter to relax, with a seemingly normal suction biopsy. 3. Biopsy. Suction, punch or open rectal biopsy is the gold standard for diagnosis. The submucosa mustbe included in the biopsyspecimen to determinethepresence or absenceof ganglion cells. Absence of ganglion cells or elevated acetylcholinesterase staining is diagnostic of Hirschsprung’s disease (91% accuracy). In ultrashort-segment disease, the aganglionic segment is limited to the internal sphincter so ganglion cells may be present on rectal suction biopsy. Excision of a strip of rectal muscle including the internal sphincter is diagnostic and therapeutic.

Management

I . Obstruction. Thisis relievedbygentle rectal washouts using warm saline till various investigations are completed. A defunctioning colostomy sited in the ganglionic bowelis commonlyperformed initially. Definitiverepair is performed between 2-6 months of age by one of five techniques, namely: Swenson’s operation (rectosigmoidectomy), Duhamel procedure (retrorectal pull-through),Soaveprocedure(endorectal pull-through), Rehbein’s procedure (resection of rectum and aganglionic bowel and dilatation of anal sphincter) and rectal myomectomy.Duhamel’sprocedure is probablythebest technique when the entire colon is affected. 2. Enterocolitis. These infants may be critically illfrom massivefluidand electrolyte losses. Resuscitatewithfluid expansion (e.g.20 mykg of FFP or albumin). correct acid-base imbalance,replacefluidand electrolytes, andcommence broad-spectrum antibiotics (including vancomycin and metronidazole). Emergency colostomy is contraindicated.

Long-term outcome

Inthemajority (85%). theoutcome for surgically treated Hirschsprung’s disease is satisfactory. Complications include disturbances of micturition (4%), anastomotic leaks(2%), anal stenosis (5-14%), prolapse, perianal abscesses, incontinence and soiling. Once enterocolitis occurs.thepatient is at increased risk ofrecurrence,evenyears after asuccessful definitive repair operation. The current mortality rate is 1-3%. Note, however. that Hirschsprung’s disease is only one of several disorders with abnormalities of the neuronal intestinal network.Inneuronal intestinal dysplasia,ganglion cells are present but in an ectopicsite. The submucosal and intermyenteric plexuses are also hypertrophied. Approximately 25% of patients withHirschsprung’sdiseasemayhaveconcomitant neuronal intestinal dysplasia.

112 HIRSCHSPRUNG’S DISEASE

Further reading Doody DP, Donahoe PK. Hirschsprung’s disease. In: Moms PJ, Malt RA (eds). Oxford Texrbook of Surgery. Oxford: Oxford University Press, 1994; 2048-52. Holschneider AM (ed). Hirschsprung’s Disease. New York Thieme-Stratton, 1982. Joseph V, Sim C. Problems and pitfalls in the management of Hirschsprung’s disease. Journal of Pediatric Surgery, 1988; 23: 398. Kusafuka T,Puri P. Altered mRNA expression of the neuronal nitric oxide synthase gene in Hirschsprung’s disease. Journal of Pediatric Surgery,1997; 32: 1054-8. Teitelbaum DH. Hirschsprung’s disease in children. Current Opinion in Pediurrics, 1995; 7: 316-22.

Tomita R,Munakata K, Kurosu Y,Tanjoh K. A role of nitric oxide in Hirschsprung’s disease. Journal of Pediatric Surgery,1995; 30: 437-40.

Related topics of interest Abdominal distension (p. 1) Neonatal surgery (p. 200) Postnatal examination (p. 244) Shock (p. 302) Vomiting (p. 331)

HIRSCHSPRUNG’S DISEASE 113

It is estimated that over 18 millionadultsand 1.5 millionchildrenworldwidehavebeen infected with HIV, and by the year 2000 over 40 million individuals (4 million children) will be infected. The HIVIAIDS epidemic now represents a formidable public health burden, particularly for developing countries. The prevalence of HIV infection among pregnant women varies from below 1.5 cases per lo00 in developed nations to an excess of 1 in 10 in some developing nations. The rate of mother-to-child (vertical) transmission of HIV is also lower in industrialized countries (14-33%) than in developing countries (22-40%). Based on some of the most recent epidemiological data (data to end-July, 1997), the prevalence of HIV infection among pregnant women in the UK was 0.19% (1 in 520) in Greater London, and 0.02%(1 in 5700) elsewhere in the UK. Approximately 300 infants are born to HIV-infected mothers each year in the UK. However, over 75% of HIV infections in pregnant women remain undiagnosedat the time ofbirth, and often women only discover they are HIVpositive when their child develops AIDS. Vertical transmission accounts for approximately 85%of cases of paediatric AIDS in the UK. These statistics and the fact that transmission of HIV from an infected motherto her child can be greatly reduced by interventions in pregnancy and in the perinatal period were recently highlighted in the recommendations of theIntercollegiate Working Partyfor Enhancing Voluntary Confidential HIV Testingin Pregnancy (Royal College of Paediatrics and Child Health, April1998).

Risk factors for HIV transmission

I . Maternal disease status e e e

Advanced maternal disease (e.g. development of clinical symptoms). Decreased CD4+ count. Increased viral load (e.g. p24 antigenaemia, positive HIV blood culture).

2. Obstetric determinants e Prolonged rupture of membranes. e Chorioamnionitis. e Vaginal delivery. e Pretenn delivery. e Post-term delivery. e Invasive intrapartum procedures.

3. Maternal immune response e e

e e

Timing of HIV transmission

e e

e

114 HIV AND AIDS

Neutralizing antibody. Cigarette smoking. Multiple sexual partners. Breast-feeding. Intrauterine (24-50%). Intrapartum (-66% in developed countries, in the absence of breast-feeding). Ingestionof blood or maternal secretion and also maternal-fetal transmission. Postnatal (I4%),mainly via breast-feeding. HIVis present in the cell-free and cellular portions of human milk with

highest concentration in colostrum. Breast-feeding doubles the rate of transmission. Transmission to infants occurs at a higher rate if the mother has a primary HIV infection duringbreast-feeding. In industrialized countries, HIVexposed infants should be formula-fed but breast-feeding may still be safer in some developing countries.

Prevention of perinatal transmission

e

e

e e

e e e

Clinical manifestations of HIV infection

Zidovudine therapy from early pregnancy through labour and for the newborn infant in HIV-infectedwomencan reduce perinatal transmission by up to 67% to around 5%. Other potentially useful anti-retrovirals as single agents or as combination therapyarecurrently undergoing evaluation. Intact fetal membranes may decrease the risk of vertical transmission. Avoid invasive procedures (e.g. scalp sampling, operative vaginal delivery) in HIV-seropositive labouring women. Passiveimmunization of motherand infant withHIV hyperimmune i.v. immunoglobulin (ACTG 185). Maternal vitamin A supplementation. HIV-seropositive mothers should not breast-feed. Ongoing trials of reverse-transcriptase inhibitors (e.g. didanosine) and active immuni7ationof mother and infant are awaited.

Signs and symptoms are rarely present in the newborn period

or first few weeks of life. 1. General. IUGR, hepatosplenomegaly.lymphadenopathy, failure to thrive.

2. Respiratoty.Pneumocyfis

carinii pneumonia (PCP), lymphoid interstitial pneumonidpulmonary lymphoid hyperplasia (LIPPLH).

3. Dermatological. Fungal, bacterial andviralskininfections. severe seborrhoeic dermatitis, vasculitis, drug eruptions. 4. Gastrointestinal. Oral candidiasis. aphthous

ulcers,

parotid gland swellings, diarrhoea.

5. Cardiovascular: Myocarditis.cardiacdysrhythmias.pericardial effusions, cardiomyopathy. 6. Neurological. Developmental delay or regression, spastic weakness of extremities. microcephaly, cerebral atrophy, basal ganglia calcification. HIV encephalopathy, seizures.

7. Renal. Proteinuria, renal failure, nephroticsyndrome. 8. Huematological. Thrombocytopenia, anaemia, leucopenia.

HIV AND AIDS 115

9. Infection. Recurrent bacterial infections, especially Streptococcus pneumonia, Salmonellasp.. Staphylococcus aureus, Haemophilus infruenzaetype b. Diagnosis of HIV infection

Early diagnosisis important for the family’s peace of mind and hasimplications for decisionsconcerningprophylaxis for opportunistic infections, intercurrent illnesses and therapeutic medicationsincluding anti-retroviral agents.However, standard HIV serological tests are not useful during the first 18 monthsbecauseofthepresence of transplacentallypassed maternal IgG. Infection in infancy can be diagnosed by either direct (detectingvirus or viralproducts) or indirect assays (detecting host responseto virus). Direct tests include HIV culture (goldstandard),polymerasechainreaction(PCR) for detection of HIV proviralDNA and p24 antigen detectionafter immunecomplexdissociation(p24-ICD) - atechniqueof freeing p24 antigen from immune complexes. Indirect assays detect intrinsically producedanti-HIVantibodies(e.g. antiHIV IgA). The sensitivity of anti-HIV IgA and IgM for diagnosingHIVinfectionduringinfancy is debatable.Direct assays are more widely used. However, in the first week of life these assays have asensitivity of only SO%, but by theage of 21 monthHIVculture or PCRhavea sensitivity anda specificity greater than 90%.

Practical approach to an HIV-exposed neonate

Perform HIV culture or PCR at 1-2 months and repeat before 6 months, but obtain a repeat sample if either test is positive. However, combining two tests does not increase sensitivity. An infant < l 8 months old maybe considered HIV-infected if helshe is HIV-seropositive, or wasborn to anHIV-infected mother and has positive results on two separate direct tests performed on separate blood samples (not cord blood). An infant is also considered HIV-infected if helshe meets the US Centers for Disease Control and Prevention (CDC) surveillance case definition for AIDS. AIDS-defining conditions include PCP, LIP/PLH, CMV, HIV encephalopathy, recurrent bacterial infections, wasting syndrome, candida oesophagitis, pulmonary candidiasis, cryptosporidiosis, herpes simplex diseaseandmycobacterium aviumintracellulare complex infection. Commence PCP prophylaxis at 4-6 weeks of age until at least 12 months of age unless HIV infection has been excluded (two or more negative direct tests performed at 21 month of age, one of which is performed at W months of age). Continue prophylaxis after I year in the presence of severe immunosup pression. Following PCP, maintain life-long prophylaxis. Prophylaxis consists of daily(or alternate day, i.e. 3 days a week)

116 HIV AND AIDS

trimethoprim-sulphamethoxazole.Alternatively. oral dapsone and monthly i.v. pentamidine may be given. Monthly i.v. immunoglobulin may reduce infectious complications in some HIV-infected children, though mortality is unaffected.

'Ikatment

Symptomatic HIV infection or asymptomatic infection with significant HIV-related immunosuppressionis an indicationfor anti-retroviral therapy(currentlynucleosideanaloguesthat inhibit viral nucleic acid synthesis by binding to the reverse transcriptase enzyme). The largest experience is with zidovudine (ZDV, AZT). Didanosine (ddI) is an alternative agent for children with advanced HIV disease and ZDV intolerance or deterioration during ZDV therapy.

Prognosis

Approximately one in five infants contractingHIVdevelop AIDS or die in the first year of life. Without anti-retroviral therapyandPCPprophylaxis,mediansurvivaltimes for infants with vertically acquired HIV infection is 3-3 years. By age 6 years, 25% of the children will have died or developed some illness because of HIV infection. PCP. especially in the first year of life, candida1 oesophagitisor severe encephalopathy indicate a poor prognosis, while low CD4+ lymphocyte counts, poor lymphocyte proliferative responses to mitogens and antigens and lack of anti-HIV neutralizing antibodies indicate rapid disease progression. Survival has improved, however, with anti-retrovirals and prophylaxis. While the long-termoutcome is notyetknown,mostinfected infants will die from AIDS or AIDS-related illnesses with only a few surviving until adulthood.

Further reading Intercollegiate Working Partyfor Enhancing Voluntary Confidential HIV Testing in Pregnancy. Reducing Mother-to-Child Transmissionof H N Infection in the United Kingdom.London: Royal College of Paediatrics and Child Health,1998. Kline MW. Vertical human immunodeficiency virus infection. In: Hansen TN. McIntosh N (eds). Current Topicsin Neonatology, Number 1. London: W.B. Saunders, 1996: 195-233. Lindsay MK. Nesheim SR. Human immunodeficiency virus infection in pregnant women and their newborns. Clinics in Perinatology, 1997; 2 4 : 161-80.

Related topicsof interest Hepatitis B (p. 105) Infection - perinatal (p. 147) Maternal drug abuse (p. 182)

HIV AND AIDS 117

HOME OXYGEN THERAPY Home oxygen therapy enables ex-preterm babies with chronic lung disease to go home from hospital weeks or months before they would ifall oxygen therapy was hospital-based and they had to wait until they werein air all the time. Such babies should have been stable on low-flow nasal oxygen for some weeks, and show no sign of coming out of oxygen in the immediate future. There are advantages to the baby. the family and the healthservice. The baby no longer has multiple caregivers, who can offer attention only when their other charges are well or sleep ing. Instead the baby gets to know hisher parents really well for the first time, as they become hisher regular providers. The home environment is more friendly and stimulating, and the baby starts to develop the normal diurnal rhythm missing in the ever-bright lights and noise of a neonatal unit. The parents feel that their baby is truly theirs to care for and bring up in their own fashion. without the 'supervision' of hospital staff. Home oxygen therapyis cost-effective carefor the health service, savingconsiderablesums of moneybytakingtheoxygendependent baby out of a hospitalcot that then bccomes availablefor another patient. Concerns about home oxygen therapy focus on the ability of the parents to cope with the 24-hours-a-day therapy, and in particular on their responses to sudden respiratory illnesses or life-threatening events. Babies with bronchopulmonary dysplasiaare at increased risk of sudden infant death. Before they agreeto take their baby home, an experienced doctor must have discussed these issues openly and honestly. Usually the parents will have seen their baby have a series of critical episodes, and be all too aware of what they are takingon. Discharge home should only be with the full support of the family doctor, health visitor, district paediatric nurse andor neonatal liaison nurse. A planning meeting to which the parents and these support workers are invited is useful. The following has to be achieved onceit is agreed that the baby should go home in oxygen: A home assessment visit is undertaken to ensure the baby can be kept warm, bathed and cared for while on oxygen therapy. The family doctor has to prescribe oxygen via nasal prongsat a specific flow rate. An oxygen concentrator with low a flow meter has to be installed in the home witha number ofoutlets to enable the babyto be cared for in two or three rooms.This equipment can only be installed once the home oxygen has been prescribed. Small portable oxygen cylinders(at least two) with low flow headsare provided. These are to enable brief outings tothe shops, relatives and clinics! Clear arrangements should exist for their replacement when empty, and the supplier must always have some full cylinders. Both parents must be shown an ARC of neonatal resuscitation. Simple mucus extractors can be provided to help the parents clear the airway (no risk of HIV transmission here). The parents must practise mouthto mouth and nose breathing and know howto check air is entering the lungs. They shouldalso practise external cardiac massage with intermittent breaths. Baby mannequins provide excellent material for teaching these skills. The only thing they needdo with their own baby is to learn how to find a radial or brachial pulse rapidly, repeatedly and reliably. A decision must be made as to whether the family should have an apnoea alarmat home (most choose to do so). This would be more for parental reassurance than any proven efficacy at preventing death, and this should be made clearto the parents.

118 HOME OXYGEN THERAPY

0 0 0 0

The family must have a telephone. The possibility of qualifying for an attendance allowance should be explored. The family must have open access to the children’s ward. Planned follow-up by health visitors and nurses is coordinated so as to avoid conflicting advice over therapy, feeding andother issues. Regular clinic follow-up and assessment is planned.

in Home oxygen therapy shouldbe continued until placing the carefully monitored baby air for periods of 30 to 60 min no longer leads to an early desaturation. If the baby’s saturations in air remain in the mid-90s in this situation, oxygen therapy should be continued until an overnight oximetry sleep study in air has been performed. Only if this is satisfactory can the continuousoxygen be stopped. The oxygenconcentratorandsmallcylindersshould be retained for a few weeks after that in case of a transient deterioration with a viral infection.

Further reading Angel1 C. Equipmentrequirements for community-basedpaediatricoxygentreatment. Archives of Disease in Childhood, 1991; 6 6 755. Samuels MP, Southall DP. Home oxygen therapy. In: DavidTJ (ed). Recent Advances in faediatrics. No. 14. Edinburgh: Churchill Livingstone, 1995; 37-51. Sauve RS, McMillan DD, Mitchell I. Creighton D, Hindle NW, Young L. Home oxygen therapy.Outcomeof infants dischargedfromNICUoncontinuoustreatment. Cfinical Pediatrics, 1989; 28: 113-8.

Related topicsof interest Bronchopulmonary dysplasia (p. 38) Discharge planning and follow-up (p. 75)

HOME OXYGEN THERAPY 119

HYDROCEPHALUS Hydrocephalus may he evident at birth (congenital hydrocephalus) or result from complications in the perinatalor postnatal period. Hydrocephalus is commonlydue to obstruction to the CSF pathways (and rarely CSF over-production) leading to dilatation of the ventricles and back pressure proximal to the site of obstruction. The most common sites of obstruction are the aqueduct of Sylvius (between the third and fourth ventricles) and the exit foramina of the fourth ventricle (the central foramen of Magendie and the two lateral foramina of Luschka). In communicating hydrocephalus, CSF can flow out of the ventricular system reaching the subarachnoid space. Communication is easilyconfirmed clinically by theriseandfall of lumbar CSF pressure on jugular venous compression (Quecken-Stedt’s test).

Aetiology

1. Congenital hvdrocephnlus. This be may single a abnormality or associated with other congenital malformations within or outside the central nervous system (CNS).

Arnold-Chiari malformation (commonly associated with myelomeningocele) obstructs the fourth ventricleforamina and occasionally the aqueduct of Sylvius. Dandy-Walker malformation (cysticdilatation of the fourthventricle) obstructs thefourthventricle foramina and occasionally the aqueduct of Sylvius. Sex-linked aqueductal stenosis confinedtomales(associated with flexion and adduction defects of the thumbs). Post-infection (toxoplasma, rubella. CMV) - cerebral atrophy may also contribute to hydrocephaly. Cerebral tumours and arterio-venous malformations. Choroid plexus papilloma (hydrocephalusfrom CSF overproduction not obstruction - rare). Secondary hydrocephalus Post-haemorrhagic (following intraventricular haemorrhage especially in preterm infants), usually comrnunicating, but with obstruction of the fourth ventricle foramina may become non-communicating. Post-infection (meningitis) due to obstruction of the aqueduct of Sylvius and the fourth ventricle foramina as well as cerebral atrophy.

Clinical features

Investigations

120 HYDROCEPHALUS

The anterior fontanelle is large or bulging with widely separated sutures and open posterior fontanellein newborn period. Other features are down-turning eyeballs (sunsetting). a head circumference exceeding the 97th centile by 2 2 cm, and the head may transilluminate.

Cranialultrasonography(mostusefulfirst-lineinvestigation)

- serial scans may be necessary.

CT scan or MRI mayberequired for moredetailed imaging. Congenitalinfectionscreen(TORCH titres if intrauterine infection suspected). For post-haemorrhagichydrocephalusinnewbornterm infants, exclude a bleeding disorder (clotting studies and platelet count) and alloimmune thrombocytopenia (mother produces immunoglobulin G (IgG) antibodies to PI*' antigen or infant's platelets).

Management

This partlydependsonthe aetiology. Congenitalhydrocephalus is probably best treated surgically by insertion of a ventriculoperitoneal or ventriculoatrial shunt. As a temporary measure if the infant is not fit for surgery, medical therapy (e.g. acetazolamide IOmglkglday) may be of value. Repeated lumbar or ventricular taps are not beneficial and are associated withahigh risk of infection. However,followingposthaemorrhagic hydrocephalus, serial CSF drainage (lumbar or ventricular taps) may be required to control rapid head growth or symptoms (apnoeas, fits) until CSF protein level is below 1g A , when a shunt may then be inserted. Shunt complications include CSF over-drainage. blockage, infection with low-grade septicaemia (Staphylococcus albus). Long-term neurodevelopmental follow-up is required.

Further reading Rayston R. Hydrocephalus Shunt Infections. London: Chapman and Hall, 1989. Levene MI. Liford W,Bennett MJ, Punt J (eds). Fetal and Neonatal Neurology and Neumsurgery. S. Edinburgh: Churchill Livingstone, 1995. Reed GB, Claireaux AE, Cockburn F (eds). Diseases of the Fetus and Newborn: Pathology, Imaging and Managing, 2nd edn. London: Chapman and Hall, 1995. Volpe JJ. Neumlogy of the Newborn, 3rd edn. Philadelphia: W.B. Saunders, 1995.

Related topics of interest Bleeding disorders (p. 25) Germinal matrix-intraventricular haemorrhage (p. 93) Head size (p. 101) Neural tube defects (p. 203)

HYDROCEPHALUS 121

Hydrops is a generalized hypoalbuminaemic oedema of the fetus and neonate. Ascites and pleural and pericardial effusions occur, and heart failure is common. It is diagnosed antenatally by ultrasound scanning with characteristic appearances - a halo of oedema, thickened subcutaneous tissues, ascites. effusionsandhepatosplenomegaly. Thereare manycauses, grouped into ‘immune’ and ‘non-immune’.

Immunological hydrops This is secondary to haemolytic disease from rhesusor other isoimmunization. It is now rare, in fewer than 1 in IOOOO deliveries because of improved antenatal care. Treatment is as for severe rhesus haemolytic disease, but with the added issues discussedbelow under emergency treatment at birth.

Non-immunological hydrops (known associations) Chromosomal

0 0

0

Cardiac

Trisomies (13, 15, 18,211. 45x0 (Turner’s). m y . Triploidy.

I . Structural 0 0 0 0 0 0

0 0 0

Septal defects. Hypoplastic left heart. Truncus arteriosus. Pulmonary atresia. Cardiac rhabdomyoma. Premature closure of ductusarteriosus. Pericardial teratoma. Subaortic stenosis with fibroelastosis. Right atrial haemangioma.

2. Dvsrhythmias 0 Supraventriculartachycardia. 0 Heartblock.

3. Othercardiac

0

0

Pulmonary

0 0

122 HYDROPS FETALIS

Myocarditis. Cardiomyopathy. Calcification of arteries or myocardium. Aspleniasyndrome. Causes of cardiac failure (e.g. arterio-venous malformation or haemangioma). Diaphragmatic hernia. Cystadenomatoidmalformation.

Tracheo-oesophageal fistula (TOF). Sequestered lung.

0 0

Infective

0 0 0

0 0

MaternaVplacental

0 0 0 0 0

0 0

Haematological

0

0

Neurological

0

0 0 0

Skeletal

0

0

Congenital tumours 0

Storage disorders

Miscellaneous

Multiple births (especially twin-twin transfusion). Diabetes. Toxaemia. True knot in cordhmbilical vein thrombosis. Vascular malformation of the cord or placenta. Biliaryatresia. Jejunalatresia. Volvulus.

Gastrointestinal

Renal

Parvovirus B 19. Cytomegalovirus. Toxoplasmosis. Syphilis. Hepatitis. Chagas' disease.

0

Congenital nephrotic syndrome. Urethral obstruction (posterior urethralvalves). Polycystic kidneys. Renalvein thrombosis. Rin-twin transfusion. Alpha thalassaemia. Fetomaternal haemorrhage. G6PD deficiency. Any fetal anaemia. Encephalocoele. Tuberous sclerosis. Agenesis of corpus callosum. Holoprosencephaly. Intracranial haemorrhage. Osteogenesis imperfecta. Some dwadisms. Teratoma. Neuroblastoma. Choriocarcinoma. Hepatoblastoma. Gaucher's disease. Niemann-Pickdisease. Mucopolysaccharidoses. Beckwith-Wiedemann syndrome. Prune belly syndrome. Myotonic dystrophy.

HYDROPS FETALIS 123

0 0

0

Neu-Laxova syndrome. Infant of a diabetic mother. Idiopathic.

It is important to remember these are some of the associations with non-immune hydrops, and that they are not necessarily the cause.

Antenatal investigation and management

Postnatal investigations and management

Isoimmunization and rhesus disease must be excluded first by investigating ABO, rhesus and other blood group antigens and haemolysins. If negative,detailed ultrasound scanning is essential, asis karyotyping and TORCH, parvovirus and venereal disease research laboratory (VDRL)screening. If samples are taken by cordocentesis, the presence of fetal anaemia and abnormal haemoglobin can be detected in addition to the other tests. Treatment as appropriate with maternal anti-dysrhythmic drugs, supportive transfusions to the fetus and possibly procedures to drain fetal ascites andpleural effusions shouldbe considered.

1. Emergency treatmentat birth Intubate and ventilate with high pressures (up to 30cmH,O). 0 Drainpleural effusions and ascites (diagnosed antenatally): keep aspirates foranalysis. 0 Insert umbilical venous lines tosecure vascular access. 0 Transfer ventilated to the neonatal unit. 0

2. On the neonatal unit 0 Insert UAC and obtain blood for baseline observations including gases, glucose, albumin, electrolytes, FBC, clotting screen,blood group and Coombs' test. 0 If a pericardialeffusion issuspected, perform cardiac echocardiography to confirm and then perform pericardiocentesis under ultrasonic guidance. 0 Get a chest and abdominal X-ray. 0 Assess the baby for congenital abnormalities: plan secondline investigations for diagnoseslisted above. 0 A s first results come back, adjust ventilation to achieve satisfactory gases, maintain blood pressure and circulation, bring central venous pressure down to 6mmHg, if necessary by withdrawing further aliquots of blood lOml at a time, and treat any metabolic acidosis as necessary. Colloid can be given slowly later, when hypoalbuminaemia has been confirmed. Long-term management

124 HYDROPS FETALIS

If the baby survives, long-term management begins with the stabilization of the baby on the ventilator. Once haematological and biochemical abnormalities have been corrected. and heart failure, pleural effusions and ascites resolved. intensive

care is discontinued. If still undiagnosed, further investigations may be necessary, and the parents should be supported and referred to a clinical geneticist. In 50% of cases, no cause is found. Mortalityis also50% or more. If the baby is stillborn or dies later, requestapost-mortemexamination. The parents should be counselled and referred to a clinical geneticist.

Further reading Fanaroff AA, Martin RJ. Neonatal-Perinatal Medicine: Diseases of the Fetus and Neonate, 6th edn. St Louis: Mosby, 1997. Hann IM. Gibson BES, LetskyEA (eds). Fetal and Neonatal Haematology.London: BaillEre Tindall, 1991. Phibbs RH. Hydrops fetalis and other causes of neonatal edema andascites. In: Polin RA, Fox WW (eds). Fetal and Neonatal Physiology. 2nd edn. Philadelphia: W.R.Saunders, 1998; 1730-6.

Reed GB, Claireaux AE, Cockburn F (eds). Diseases of the Fetus and Newborn: Pathology, Imaging, Genetics and Managing, 2nd edn. London: Chapman & Hall Medical, 1995. Stephenson T,Zuccollo J, Hohajer M. Diagnosis and managementof non-immune hydrops in the newborn. Archives of Disease in Childhood, 1994; 70: F151-4.

Related topics of interest Anaemia (p. 9) Cardiac arrhythmias (p. 43) Haemolytic disease (p. 97) Respiratory distress (p. 275) Resuscitation (p. 282)

HYDROPS FETALIS 125

Most floppy babies do not have a persistent neuromuscular disorder. They may have benign neonatal hypotonia - characterized by a floppiness with normal strength - or a transient hypotonia related to conditions such as prematurity or mild birth asphyxia (stage 1 hypoxicischaemic encephalopathy). Hypotonia is classified 'anatomically' in a centrifugal fashion: that is, as central in origin. or from the spinal cord, the peripheral nerves, the neuromuscular junction or the muscles themselves.

I . Primant

hypotonia Central

e e e 0

e

Down's syndrome. Prader-Willi syndrome. Peroxisomal disorders. Cerebral palsy - the hypertonia develops later. Brain malformations.

2. Secondary Anaesthesia. e Drugs, e.g. maternal benzodiazepines. e Sepsis. e Respiratory distress. 0 Hypoglycaemia. e Metabolic disorders.

e

Spinal cord

disorders

e e

Peripheral nerve abnormalities Neuromuscularjunction disorders

e e 0

e

e

Muscle disease

Birth injuries to the cervical spine and cord. Spinal muscular atrophy - type 1 (Werdnig-Hoffman).

is very rare in neonates. Ageneralized peripheral neuropathy Local palsies secondary to trauma are easily recognized. Transient neonatal myasthenia - anti-acetylcholine receptor antibodies cross the placenta. Feeding and respiratory difficulties - usually respond to neostigmine, ventilation occasionallyneeded.Improvement after dayslweeks. Congenital myasthenic syndromes.

1. Congenital musculardystrophy. Weak, with contractures1 arthrogryposis. Many improve slowly. Several subgroups are now recognized(see 'Neuromuscular disorders- muscular').

2. Myotonic dystrophy. The mother is always affected. Symptoms are polyhydramnios secondary to swallowing difficulties in utero; immobile face, triangular mouth, respiratory difficulties; not myotonic as a baby. Many have learning difficulties andsomehave gut, and later CNSandendocrine involvement. 3. Congenital myopathies. Symptomsincludehypotonia, respiratory difficulties and later learning difficulties. Riochem-

126 HYPOTONIA

ical abnormality has yet to be clarified in many types, and diagnosis is usually by muscle biopsy.

Investigation and management

As is evident from the above lists, the causes of neonatal hypotonia are legion. The approach to investigating hypotonia is determined to a large part by the clinical impression of the suspected underlying cause(s). Theinvestigation and management of the various disorders are outlined under the relevant topics. Detailed accounts on neuromuscular investigations have been set out under ‘Neuromuscular disorders’.

Further reading Crawford TO. Clinical evaluation of the floppy infant. Pediatric Annals,1992; 21: 348. Curran A, Jardine P. The floppy infant. Current Paediatrics, 1998: 8: 37-42. Dubowitz V. The Floppy Infant, 2nd edn.Clinics in Developmental Medicine No.76. Cambridge: Cambridge University Press, 1980. Dubowitz V. Muscle Disorders in Childltood,2nd edn. London: W.R. Saunders, 1995. Roper HP. Neuromuscular diseases in children. British Journal of Hospital Medicine. 1993; 49: 537-45.

Related topics of interest Assessment of gestational age (p. 19) Birth injuries (p. 21) Feeding difficulties (p. 84) Hypoxic-ischaemic encephalopathy (p. 128) Inherited metabolic disease - investigation and management (p. 156) Neurological evaluation (p. 206) Neuromuscular disorders - muscular (p. 210) Neuromuscular disorders - neurological (p. 214)

HYPOTONIA 127

HYPOXIC-ISCHAEMIC ENCEPHALOPATHY The term birth asphyxia is poorly defined, but includes decreased oxygen delivery to, and perfusion of. vital organs, particularly the brain. It is associated with metabolic acidosis, low Apgar scores and end organ damage. Many authorities feel the term should no longer be used and more objective mea..ures should be recorded (e.g. umbilical cord blood gases). Although birth asphyxia is a multi-system disorder. it is the effect on the brain - the post-asphyxial encephalopathy - which is ofprimeimportancein the outcome.Post-asphyxial or hypoxic-ischaemic encephalopathy (HIE) is a variable constellation of symptoms and signs, including alterations in consciousness and behaviour, feedingdifficulties. abnormal tone, convulsions and failure to maintain regularrespiration. About 1 in 500 term babies hasHIE severe enough to cause fits or coma.

Prognostic evaluation

Early prediction of prognosis in each case of perinatal asphyxia and HIE is important. Accurate information should be given to parents, for starting resuscitation or withdrawing therapy, and in the future, the possibility of offering effective neuroprotective therapy. Prognostic statementsfor infants with HIE are best made from the level of severity of theclinical syndrome. Two main classifications are in use and their features are summarized in Tables I and 2.

Table 1. Samat and Samat classification of HIE Stage 1

Stage 3

Stage 2

Hyperalert Consciousness Seizures decerebration tone Muscle Duration

EEG

c24 hours

Common: focal multifocal Hours 2-14 days

or

Uncommon: excluding

to weeks

with pattern Periodic changes: Variable Normal seizures 20X 103/mm3. neutrophils -3or >l0 X 103/mm3or immature leucocytes (band cells) with toxic granulation and thrombocytopenia suggest sepsis. Blood cultures. Urine culture suprapubic aspirate or clean catch specimen (onmicroscopy,eightorganisms per highpowerfield suggests infection). Surface swabs of ear, nose, throat and umbilicus. Microscopy and Gram stain, culture and virology (? electron microscopy for virus particles). Stools for bacteriology and virology.

-

140 INFECTION GENERAL

CSF for microscopy and Gram stain, culture and sensitivity, virology and biochemistry (protein> l S-2.0gfl in term infants and >3.7 g4 in preterm infants, CSF glucose 4 0 % of blood glucose or l white cell per 500 red cells (traumatic samples) or >20-30 polymorphonuclear ~eucocytes/mm~ (atraumatic samples), all suggest meningitis). CSF serology for group B streptococcal or E. coli antigen. Clotting screen (when bleeding present or serious infection suspected). Blood gases, glucose, U&E. C-reactive protein (CRP). Chest radiograph@) and abdominal radiograph@), in the presence of abdominal signs. Abdominal ultrasound (intra-abdominal masses and sepsis, renal and urinary tract infection, ascites).

Management

Commence broad-spectrum i.v. antibiotics immediately. In general,ifculturesarenegativeandthe infant is well, antibiotics may be discontinued after 48-72 hours. Where cultures are negative but a temporal improvement in the infant’s condition is noted with antimicrobial therapy,therapy is continued for 5-7 days. If sepsis is confirmed by positive culture(s). therapy is continued for atleast 10days and occasionally longer depending on the focusof infection (e.g. brain or bone) and the isolated pathogen. In sick infants, commence continuous monitoring of physiological parameters including transcutaneous oxygen saturations by pulse oximetry. Commence assisted ventilation for recurrent apnoeas and respiratory failure. Monitor arterial blood gases 4-&hourly in infants with respiratory distress or receiving assisted ventilation. Monitor BP byanindwelling arterial device or noninvasivelyregularly (l-bhourly) in all ill andunstable infants, more frequently in sicker infants. Correcthypotensionwith FFP (10-15mVkg) andadd inotropes(dopamine/dobutamine at 10-20 pgkglmin) if BP still suboptimal. Administer i.v. dextrosesolutions to maintainnormal blood glucose and electrolytes (check U&E). Monitorthecore-peripheraltemperature gap in sick infants as a guide to the adequacy of tissue perfusion. Modify drug therapy according to the evolution of the illness, taking into account reports from bacteriology (pathogens isolated and their sensitivity).

INFECTION - GENERAL 141

Further reading Gerdes JS. Clinicopathologic approach to the diagnosis of neonatal sepsis. Clinics in Perinatofogy. 1991; 18: 361-81. Isaacs D, Moxon ER. Neonatal Infections. Oxford: Butterworth-Heinemann. 1991. Klein JO, Remington JS. Current concepts of infections of the fetus and newborn infant. In: Remington JS, Klein JO (eds). Infectious Diseases of the Fetus and Newborn Infant. 4th edn. Philadelphia: W.B. Saunders, 1995; 1-19. Lewis DB. Wilson CB. Developmental immunology and role of hostdefenses in neonatal susceptibility toinfection. In: Remington JS, Klein JO (eds). hfectious Diseases ofthe Fetus and Newborn Infant. 4th edn. Philadelphia: W.B. Saunders, 1995; 20-98. Powell KR, Marcy SM. Laboratory aids for diagnosis of neonatal sepsis. In: Remington JS, Klein JO (eds). Itfectious Diseases of the Fetus and Newborn Infant. 4th edn. Philadelphia: W.B. Saunders, 1995; 1223-40.

Related topicsof interest Acute collapse (p. 6) Apnoeas and bradycardias (p. 16) Infection - neonatal (p. 143) Infection - perinatal (p. 147) Infection - prenatal (p. 15 1) Respiratory distress (p. 275) Resuscitation (p. 282) Shock (p. 302) Transfusion of blood and blood products (p. 323)

142 INFECTION - GENERAL

INFECTION

- NEONATAL

Neonatal infections may be acquired at birth but with a late presentation (after 3 days), or be acquired postnatally as nosocomial infections. This section covers the traditional 'late-onset' infections, i.e. those occumng after the first week of life. Untreated, infections in newborns can become life-threatening. It is important, therefore, that infections in newborn infants be identified and treated promptly. The globalburdenofneonatalinfections is substantial. Worldwide, some30 million infants develop an infection in the neonatal period and infants five die from neonatal infection every minute. The organisms associated with neonatal infections vary significantly in different geographical areas. Thus while group B streptococcus (GBS) continues to be the most important bacterial pathogen associated with early-onset sepsis in many developed countries, for reasons which remain unclear, neonates in some developing nations are rarely infected with GBS, which only accounts for 1 4 % of neonatal infection. Neonatal infections in the developing nations are dominated by Gram-negative Klebsiella (e.g. sp.) and Gram-positive organisms (e.g. Staphylococcus aureus). It is therefore essential that antibiotic therapy be tailored to the specific microbial needs of a particular geographical region.

General infections Common causative organisms

Bacterial infections Staphylococcus epidermidis. Escherichia coli. Streptococcus. Staphylococcus aureus. Pseudomonas aeruginosa. Entembacter cloacea. Klebsiella. Pmteus.

2. Viralinfections 0

Respiratorysyncytialvirus(RSV). Enterovirus. Echo virus.

3. Other Candida. Chlamydiatrachomatis. Risk factors

0

0 0

0

Prematurity. Intubation. Centralintravascularaccess. Recent surgery (including drains in situ). Indwelling peripheral arterial and umbilical catheters. Congenital anomalies (urinary tract, gastrointestinal, spinal). Presence of infectious organism in other patients, parents or staff.

-

INFECTION NEONATAL 143

Clinical presentation

Commonly presents as:

e

Investigations

Septicaemia. Oral and perineal thrush. Snuffles. sticky eyes and coughing. Pneumonia (intubated infants, aspiration). Meningitis (apnoeas, seizures). Diarrhoea. Urinary tract infection (vomiting, feeding intolerance). Osteomyelitis (immobile, oedematous inflamed and tender limbs or joints). Cardiac failure (myocarditis with cyanosis, poor cardiac output, hepatosplenomegaly).

I . General A full septic screen. Always culture urine - clean catch or suprapubic aspirate. ECG - suspectedmyocarditis(lowvoltagecomplexes and arrhythmias). Renalandbladderultrasoundscan - UTI. For suspectedosteomyelitis aspirate fluidfrominfected bone or joint and obtain radiographs.

2. Special Cranial CT or MRI scans (CNS sepsis). Boneisotopescans. Labelledleucocytescans.

Management

Antibiotic choice for pneumonia. septicaemia, or meningitis depends on the local microbiological flora. Commonly acombination of penicillin or ampicillinwith an aminoglycoside (usually gentamicin) will suffice until microbial culture reports are available. The antibiotic choice may be modified depending on the sensitivities of the isolated organisms.

Specific infections Staphylococcal infections Staphylococci belong to the family Micrococcaceae and can be differentiated into two large groups on the basis of their ability to fermentmannitolandproduce the extracellular enzyme coagulase. Organisms able to ferment mannitol and produce coagulase are called coagulase-positive organisms or Staphylococcusaurens. Organisms negative for these products are calledcoagulase-negativestaphylococci,themostimportant being Srapl~vlococcus epidennidisand Staphylococcus saprophyticus. Gram stain showsGram-positive cocci. Inrecent years coagulase-negative staphylococci have assumed predominance as NICU pathogens. Infants are colonized by coagu144 INFECTION - NEONATAL

lase-negative staphylococci and S. aureus soon after birth and mostly by staff contact. Hand washingis one of the most effective means of reducing colonization. The virulence ofS. aureus is related to the production of coagulase, alpha-haemolysin and leucocidin whereas coagulase-negative staphylococci produce polysaccharide a mucoid (slime) which facilitates their adherence to foreign bodies (e.g.catheters) and hinders phagocytosis. S. aureus causes the following infections: Impetigo. Staphylococcal scalded skin syndrome. Chronic recurrent furunculosis. Eye, ear, nose and throat infections. Breast abscesses. Septicaemia. Pneumonia. Osteomyelitis. Septic arthritis. Endocarditis (rare, more likely withcoagulase-negative staphylococci and intravascular catheters). Coagulase-negative staphylococci are an important cause of nosocomial infection, especially in VLBW infants, and risk of infection is increased in the presence of indwelling medical devices(e.g.venouscatheters or central nervoussystem shunts). S. epidermidis is themostfrequent bacterial speciesisolated from blood. S. aureus andcoagulase-negativestaphylococci are now widely resistant to penicillin G due toR-lactamase production. Inrecentyearsresistance to semisyntheticB-lactamase resistant penicillins (e.g. methicillin) has produced problematicinfectionswith methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci. Once introducedintoa hospital, MRSA are difficult to eliminate.

Treatment. First-line agents for methicillin-susceptible strains

of S. aurells include flucloxacillin. oxacillin, and some ‘first generation’cephalosporins(e.g.cephalexin).Glycopeptide antimicrobials (e.g. vancomycin. teicoplanin) are the agents of choice for methicillin-resistant staphylococcal infections, and coagulase-negativestaphylococciinfections resistant to the common first-line drugs.

-

INFECTION NEONATAL 145

Respiratory syncytial virus (RSV)

RSV is apneumovirusofthefamilyParamyxoviridaeofwhich two types (A and B) exist. It causes annual outbreaks ofinfection (bronchiolitis) during the winter months. The incubation period is 2-8 days withviralshedding lasting 3-4 weeks. Spread is by aerosol or direct contact with infected secretions.

0

Clinical features include upper respiratory tract symptoms (coughand rhinitis) followedbylowerrespiratory tract symptoms (tachypnoea, recessions and cyanosis). Symptomsanddisease severity areage-dependent. The veryyoung ( l 2 weeks, especially preterm infants with chronic lung disease who are morelikely to require assisted ventilation. Infantswithcongenitalheartdisease(CHD) are alsoat high risk for severe disease (more likely to require supplemental oxygen (83%), intensive care (308), assisted ventilation (19%) and die (3.4%)). Diagnosis is by direct fluorescentantibodydetection of virus and enzyme-linked immunosorbent assays of nasopharyngeal aspirates. Therapy is mainlysupportive (fluids, supplemental oxygen, antibiotics for pneumonia) with ribavirin being given early to the high-risk groups (BPD, CHD). HyperimmuneRSVimmunoglobulin,e.g. RespiGamTM (Medimmune Inc, Gaithersburg, MD, USA), is effective prophylaxis for preterm infants (c36 weeks' gestation and age 24 hours) rupture of membranes. Cloudy or foul-smellingliquor. Instrumentaldelivery. Prematurelabour. Longlabour.

Clinicalfeatures

These vary from non-specific signs to obvious signs of sepsis with pallor and shock. See ‘Infection - general’.

Investigations

e e e 0

e 0

e e

Management

e

FRC. CRP. Chest X-ray. Blood and CSF culture. GBS antigen in urine and CSF. Coagulation studies in severe sepsis. Virus identification by electron microscopyin vesicle fluid, PCR, or serology. Chlamydia - direct immunofluourescence test andspecific IgM. For symptomatic infants perform a full septic screen and commence broad-spectrum antibiotics (commonly ampicillidpenicillin and an aminoglycoside).

INFECTION - PERINATAL 147

For asymptomatic infants perform a septic screen (omitting

lumbar puncture) followed by broad-spectrumantibiotics. Discontinue antibiotics ifbacteriologyshows no growth at 48 hours and theinfant is well. However, continue antibiotics for at least 5 days ifthemotherreceived antibiotics intrapartum.

Specific infections Group B streptococcus

In the developed nations, GBS disease is the commonest cause of fatal bacterial infection in newborns. A quarterto a third of all adults carry GBS. It is found primarily in the gastrointestinal tract but also in the genital tract where it is usually asymptomatic. At birth -25% of mothers have GBS in their genital tract. Early onset infection (which constitutes60%of all GBS infection) is largely acquired from the maternal genital tract. The US average incidence is -1.4 per lo00 births, while in the U K it is 0.5-0.7 per 1000 births. The majority of early onset infections occur in utero and are therefore not influenced by mode of delivery.

1. Risk factors for GBs infection Prolonged rupture of membranes. e Intrapartum pyrexia (>37.8"C). e Preterm rupture of membranes (PROM). e Preterm labour (90% of congenital infection. The congenitally infected infant may be mildly affected witheye involvement only,or severely affected with skinlesions, chorioretinitis and microcephaly (or hydranencephaly). Diagnosis is by virus culture (urine, stool, blood, CSF, vesicle fluid, conjunctival scrapings, and swabs of theeye, throat andrectum), light microscopy(intranuclear inclusions) or electron microscopy of conjunctival scrapings, and PCR to detect HSV DNA (e.g. in CSF and serum). EEG mayshowlocalizingsignsofhigh-voltagelow-frequency activity, and CT or M M scans may show temporallobe necrosis or haemorrhage. Treatmentis with acyclovir(or vidarabine) with full intensive care support. Mortality is 15% with CNS involvement,and 57% withdisseminateddisease.Rarely, infants with congenital HSV develop normally.

Other infections Syphilis

Infected newborn infants may appear normal or be severely affectedwithextensiveskineruptionsthrough to marked hydrops fetalis. Allpregnantmothersshould be screened (VDRL, TPHA or ELISA) for syphilis. False positives may occur after Treponemaperienue infection(yaws).Maternal

INFECTION

- PRENATAL 153

infection leadsto intrauterine infection in up to half of all pregnancies with increased fetal loss from abortions or stillbirths.

I. Clinical features e e

e e e e e

e e e

e e

Infant mayinitially appear normal, with signsonly appearing weeks to months later. Extensive mucocutaneous lesions in the absence of systemic disturbancebutwithhepatosplenomegalyandlymphadenopathy. Severe systemic disturbance but without the typical skin rashes. Cutaneous manifestations (maculopapular rash with circinate lesions involving palms and soles offeet). Rhinitisfollowed by mucopurulentblood-stainednasal discharge. Destruction of nasal cartilage and bone produces flattened nasal bridge and saddle nose. Fissuresandbleedingfromlesions at mucocutaneous junctions. Rhagades. Condylomata around anus and female genitalia. Osteochondritis, especially wrists, elbows and knees. Periostitis, especially in limb bones and skull. Meningitis and hydrocephalus.

2. Investigations e FBC. e Liver function tests. e Syphilis serology (VDRL, TPHAor ELISA with rising or persistently high titres). e Dark-field microscopy of fluid from skin lesions and nasal discharge. e Radiography of long bones(periostitis and osteochondritis). e CSF examination (lymphocytosis, raised protein, normal glucose level, syphilis serology positive). 3. Management. Take precautions as skin lesions are infectious. Procaine penicillin 30mgkg/day i.m. for 10 days or singlei.m. injection of long-acting benmthine penicillin 60mgkg. Treat mother andpartner(s)!

Varicella-zoster

Varicella-zoster virus (VZV) infection during pregnancy(incidence -0.7 in IOOO), particularly during the first 20 weeks, may result in fetal loss or congenital varicella-zoster syndrome, withcutaneouslesions (scars) (70%), ocularabnormalities (chorioretinitis, microphthalmia, cataracts, Homer’s syndrome), CNS lesions (50%) (cortical atrophy. calcifications, mental retardation), and abnormal limb development (hypoplasia, abnormal or absent digits). Administration of varicella-

154 INFECTION - PRENATAL

zoster immunoglobulin (VZIG) post-exposure mayprevent fetal infection, and acyclovir therapy during pregnancy may be safe.

Parvovirus B19

Parvovirus B19, the causative agent of erythema infectiosum (Fifth's disease),has a predilection for bone marrow erythroid precursors. Lysis of theerythroid precursors is responsible for decreased red cell production. The incidence of B 19 infection during pregnancy is reported as 3.7% with a vertical transmission of 16% during thefirst 20 weeksand35% after 20 weeks gestation. Infection-related fetal loss is low at 0.6 per lo00 women, The commonest symptomatic presentation of prenatal infection is non-immune hydrops secondary to severe fetal anaemia, but this only occurs in -1% of infected infants. Most infants with prenatal B19 infection are normal. No studies support a correlation between maternal infection and an increased risk of birth defects. Diagnosis is by electron microscopy of virions in tissue specimens, detection of viral DNA by PCR or serology (IgM and IgG antibodies). Negative IgM assay at birth does not rule out congenital infection.

HIV infection

Approximately 8% to 24-50% of the total HIV vertical transmission is estimated to occur in urem. Vertical transmission is reduced by prenatal, perinatal and early neonatal zidovudine therapy. No HIV-associated dysmorphic syndrome exists.

Further reading Greenough A, Osborne J, Sutherland S (eds). Congenital,Perinatal and Neonatal Infections. Edinburgh: Churchill Livingstone, 1992. Remington JS, Klein JO (eds). Infectious Disease of the Fetus and Newborn Infant, 4th edn. Philadelphia: W.B. Saunders, 1995. Stoll BJ, Weisman LE (eds). Infections in Perinatology. In: Clinics in Perinatology, 1997; W1).

Related topics of interest Congenital malformations and birth defects (p. 70) Infection - general (p. 139) Infection - neonatal (p. 143) Infection - perinatal (p. 147) Intrauterine growth restriction (p. 165) Prenatal diagnosis (p. 253)

INFECTION

- PRENATAL 155

INHERITED METABOLIC DISEASE INVESTIGATION AND MANAGEMENT As over a hundred inherited metabolic diseases (IMDs) can present in newborn

infants, it would be impractical to cover these disorders in any detail in a brief synopsis. A summary of an approach to the investigation and management of IMDs may be more useful. The diagnosis of IMD has implications for future pregnancies, as prenatal diagnosis is now possible for many of these conditions. Although IMDs may present in a myriad of ways, certain details offer important clues to the possibility of IMD, namely unexplained neonatal deaths, a previously affected sibling or close relative, and consanguinity. A history of sudden illness in a previouslywell infant (particularly whenvomiting,acidosisandcirculatorydisturbance are followed by depressed consciousness and convulsions or neurological features out of proportion to the perceived insult) are alsohighly suggestive of IMD. For simplicity, IMDs may be dividedinto three groups.

Group 1

These disorders lead to toxicity from accumulation of compounds proximal to the metabolic block, for example aminoacidopathies, organic acidurias, urea cycle defects and sugar intolerances. There is a symptom-free period followedby signs ofacuteintoxication(e.g.vomiting,lethargy,coma,etc.). Metabolic disturbances arc common (hypoglycaemia, ketosis, acidosis, hyperammonaemia. etc.). Diagnosis relies on the assay of urine and plasma amino acids and organic acids. Therapy entails removal of toxic compounds by extrarenal procedures or special diets.

Group 2

These disorders arise partly fromadefectin utilization or production of energy due to a metabolic defect in the liver, muscle,myocardium or brain, for exampleglycogenosis types I and III, congenital lactic acidaemia, fatty acid oxidation defects andmitochondrialrespiratorychain defects. Symptoms include hypoglycaemia, hyperlactacidaemia, severe hypotonia,myopathy,cardiomyopathy,cardiac failure and sudden infant deathsyndrome.Thesedisordersmay arise antenatally.

Group 3

These disorders disturb the synthesis or catabolism of complexmolecules.Symptoms are permanent,progressiveand not related to food intake, e.g. lysosomal disorders, peroxisomaldisorders,a,-anti-trypsindeficiencyandcarbohydratedeficient glycoprotein (CDG) syndrome. As therapies are not available for most of these conditions, ascertaining the correct diagnosis is important.

Presentation of IMD in the neonatal period

For simplicity, three presentations may be described: neurological, hepatodigestive and cardiac.

1. Neurologicalpresentations. These may present primarily as hypotonia, seizures or neurological dysfunction.

156 IMD - INVESTIGATION AND MANAGEMENT

(a) Neurological dysfunction In group 1 (toxicity) disorders, there is often a normal pregnancy and delivery, an initial normal and symptom-free postnatal period, followed unprovoked by progressive deterioration unresponsive to symptomatic therapy. Typically theaffected infant feeds poorlyandthenprogresses into a comawithapnoeas,bradycardias,hiccupsandinvoluntary movements (tremors, myoclonic jerks), axial hypotonia and limb hypertonia. In group 2 (energy deficiency) disorders, there is no interveningsymptom-freeposmatalperiod.Commonlythere is generalized hypotonia, rapidly progressive neurological deterioration, hypertrophic cardiomyopathy, occasional malformations and dysmorphic features. (b) Seizures Seizures occur as early signs of IMD in pyridoxine dependency,sulphiteoxidasedeficiency,non-ketotichyperglycinaemia (NKH) and peroxisomal disorders. Of note, seizures rarely occur in organic acidurias or urea cycle defects unless the affected infant is comatose, hypoglycaemic or in a preexisting stupor. (c) Hypotonia Predominant or isolated hypotonia is only seen in a fewIMDs (e.g. peroxisomal disorders, NKH, respiratory chain disorders, sulphite oxidase deficiency and urea cycledefects).

2. Hepatodigestive presentations. Hepatomegaly with hypoglycaemia and seizures suggest glycogenosis types I and 111. fructose diphosphatase deficiencyor hyper-insulinism. Liver failure syndrome(jaundice,haemorrhagicdisease, hepatocellular necrosis with raised transaminases, ascites and hypoglycaemia) suggests galactosaemia, fructosaemia, tyrosinosis type I (after 2-3 weeks), neonatal haemochromatosis and respiratory chain disorders. Primarilycholestatic jaundice with failure to thrive is observedina,-anti-trypsindeficiency, bile acidmetabolic defects, peroxisomal disorders, Niemann-Pick type C disease, CDG syndrome, and Byler’s disease. Hepatic presentations of fatty acid oxidation defectsor urea cycle defects consist fatty of degeneration or Reye-like syndrome with slightly prolonged prothrombintime,raisedtransaminases,normal bilirubin levels but not true liver failure. 3. Cardiac presentations. Cardiac failure withcardiomyopathy (dilated hypertrophic), hypotonia, muscle weakness and failure to thrive suggests Pompe’s disease, respiratory chain disorders, fatty acid oxidation defects or CDG syndrome. Longchain fatty acid oxidation defects may present with conduction

IMD

- INVESTIGATION AND MANAGEMENT 157

defects (A-V block, bundle branch blocks, ventricular tachycardia).

Investigations

Investigations must proceed alongside supportive therapy. Certain findings may be especially significant in suspected IMD, namelymetabolicacidosiswithlargeanion gap (organic acidurias), acetonuria(alwaysabnormalinnewborn),and raised lactate concentrationwithketosis(especially in the absence of hypoxic insult, infection or circulatory collapse). Hyperammonaemia often suggests a urea cycle defect (with associatedrespiratory alkalosis). organicacidaemia(with ketoacidosis) or transient hyperammonaemia in pretem infants. Leucopenia, thrombocytopenia and even sepsis may also be present, especially in organic acidurias. Obtain adequate amounts of plasma, urine andCSF forimmediate analysis and storage. Expert metabolic advice is essential.

1. Urine Notesmelland colour. Reducingsubstances (Clinitest, Ames). pH(pH stix, Merck). Acetone(Acetest,Ames). Keto acids (dinitrophenylhydrazine(DNPH)). Sulphitest(Merck). Uric acid. Electrolytes. Organicacidchromatography. Each fresh urine sample should be collected separately and either frozen (-20°C) for storage or kept in the fridge if not being assayed immediately.

2. Blood FBC. Blood gases. Blood glucose. Ammonia. Liver function tests (including transaminases). Coagulation screen. Amino acid chromatography. Electrolytes (check anion gap), calcium. Lactate and pyruvate. Uric acid. Free fatty acids. Acetoacetate, 3-hydroxybutyrate. For storage, obtain 5 ml of heparinized plasma and freeze (-2OoC), and freeze whole blood (10mI in EDTA tube)for DNA studies. In addition, obtain blood onfilter paper (Guthrie test cards). For white and red cells, spin the blood sample,

158 IMD

- INVESTIGATION AND MANAGEMENT

separate the plasma and store frozen ( -2O"C), keeping the infranatant (red and white cells) at +4"C (for up to 2 days).

3. Other investigations 0

0

0

0 0 0 0

Management

Lumbar puncture (CSF biochemistry, store some CSF at -20°C). Skin biopsy (fibroblast culture) - place in culture medium or normal saline and store at +4"C. Liverand muscle biopsies (before or after death). Freeze the liver biopsy tissue immediately on dry ice or in liquid nitrogen. Cerebral ultrasound and EEG. Fxhocardiography andECG. Chest X-ray. Post-mortem.

1. General. The primary goalis to correct the biochemical derangement(s)while ensuring adequate nutrition. The production of toxicmetabolites should be suppressed while encouraging theirelimination by extrarenal andalternate pathways. Supportive care is required and this includes mechanical ventilation, circulatory support, maintenance of good hydration and diuresis with correction of electrolytes, correction of severe acidosis (pH C7.15) and treatment of sepsis.

2. Specific therapies. Peritoneal dialysis, haemodialysis and exchange transfusion (with fresh blood) may be useful in some IMDs where the accumulation of toxic metabolites is detrimental (organic acidurias, urea cycle defects).Adequate nutrition suppresses endogenous tissue breakdown. At the earliest opportunity, enteralor total parenteral nutritionshould be commenced using appropriate glucose, lipid and amino acids, and mixtures built up to provide the recommended dietary allowance (RDA). Insulin infusion (0.2-0.3 unitskghour) may suppress catabolism. Sodium benzoate (250-500mglkg/day) and sodium phenylbutyrate (250-650 mg/kg/day) may be useful in urea cycle defectsby enhancing nitrogen excretion as hippurate and phenylacetylglutamine, respectively. Arginine becomes an essential amino acid in urea cycle defects and therefore requires supplementation (at doses of 100-150 mg/kg/day) tomaintain plasma concentrations of 50-200 FmoV1. Alternatively. substitute citrulline (up to 700 mglkglday) for arginine. L-carnitine (100mg/kg/day), orally or intravenously,is useful in organic acidaemias (propionic,isovalericand methylmalonic acidaemias, and 3-methylcrotonyl glycinuria) as it enhances specific acylcarnitine excretion.

IMD - INVESTIGATION AND MANAGEMENT 159

0

Long-term outcome

Dichloroacetate (DCA), a potent inhibitor of pyruvate dehydrogenase kinase, is useful in congenital lactic acidosis unresponsive toother therapies. All severe hyperlactacidaemias (primary or secondary) are DCA responsive (50 mg/kg/day).

Despite several advances in the diagnostic techniques for these disorders, the long-term outlook remains largely poor. Most patients with urea cycle defects and hyperammonaemia have a very poor outcome, with most survivors being handicapped. Those known to be affected prenatally may initially do better if treated expectantly, but a favourable long-term outlook may only be secured by livertransplantation. The organic acidaemias generally have a poor outcome and affected infants mayonlybenefitsignificantlyfromlivertransplantation or futuristic gene therapy. Isovaleric acidaemia has a better outlook than the other acidaemias, with neurodevelopmental outcome depending onearly diagnosis and compliance with treatment. With early diagnosis and meticulous therapy, infants with maple syrup urine disease (MSUD) can be expected to survive long-term with at times satisfactory neurodevelopmental outcomes. The excellence of long-term metabolic control and the length of time after birth for which the plasma leucine levels are above 1 mmoVl directly influence intellectual outcome.

Further reading Chaves-Caballo E. Detection ofinherited neurometabolic disorders: a practical clinical approach. Pediatric Clinicsof North America, 1992; 39: 801. Greene CL, Goodman SI. Inborn errors of metabolism. In: Hay WW, Groothuis R,Hayward AR et a1 (eds). Current Pediatric Diagnosis and Treatment,13th edn. Stamford: Appleton & Lange, 1997; 864. Ogier de Baulny H, Saudubray JM. Emergency treatments. In: Fernandes J, Saudubray JM, Van den Berghe G (eds). Inborn Metabolic Disease: Diagnosis and Treatment, 2nd edn. New York: Springer-Verlag. 1995; 47-55. Saudubray JM, Narcy C, Lyonnet L et al. Clinical approach to inherited metabolic disorders in neonates. Riology of the Neonate, 1990; 58:44. WerlinSL. E. coli sepsis as a presenting sign in neonatal propionic acidemia. American Journal of Medical Genetics, 1993; 46: 455.

Related topics of interest Acute collapse (p. 6) Death of a baby (p. 72) Inherited metabolic disease recognizable patterns (p. 161)

Prenatal diagnosis (p. 253)

160 IMD - INVESTIGATION AND MANAGEMENT

INHERITED METABOLIC DISEASE RECOGNIZABLE PATTERNS Several clinical signs and laboratory findings are especially valuable in diagnosing metabolic IMDs. The following patterns may be recognized.

Alteredneurological status

1. Toxic type with hypertonia andabnormalmovements investigations (a) Principal Urine and plasma amino acid chromatography. (b) Findings Urine DNPH strongly positive, no acidosis and minor or no acetonuria.Normal lactate, glucoseandcalcium. Ammonia normal or raised. (c) Usual diagnosis MSUD (characteristic smell).

2. Toxic type with dehydration (a) Principal investigations Urine and plasma organic acid chromomatography, plasma and urine carnitine esters and plasma carnitine. (b) Findings Moderate acetonuria and acidosis. Urine DNPH slightly positive or negative. Ammonia raised. Lactate normal or raised, glucose and calcium normal or raised. Leucopenia and thmmbocytopenia. (c) Usual diagnoses Ketolytic defects, organic acidurias (isovaleric acidaemia, propionic acidaemia, methylmalonic acidaemia).

3. Energy deficiency type with liver orcardiac symptoms (a) Principal investigations Plasma and urine organic acids, plasma carnitine, loading or fasting test, fatty acid oxidation studies on lymphocytes or fibroblasts. (b) Findings AcidosiswithoutacetonuriaandurineDNPHnegative. Lactate and ammonia raised with lowlnormal calcium or glucose and normal blood count. (c) Usual diagnoses Fatty acid oxidation andketogenesisdefects. 4. Eneqp deficiency type, hypotonia, tachypnoea (a) Principal investigations Lactatelpyruvate ratios, hydroxybutyratelacetoacetateratio, urine organic acids, enzyme assays (muscle, fibroblast or lymphocytes).

IMD - RECOGNIZABLE PATTERNS 161

(b) Findings Marked acidosis, acetonuria and lactacidaemia. Ammonia normal or raised. Normal calcium and glucose. (c) Usual diagnoses Multiple carboxylase deficiency, congenital lactic acidosis (pyruvatecarboxylase,pyruvatedehydrogenase,Krebs cycle, respiratory chain).

5. Toxic type, hypotonia, seizures, coma and moderate hepatocellular disturbances (a) Principal investigations Plasma and urineamino acids, urine organic acids, liver or intestinal enzyme studies (e.g. ornithine carbamyl transferase and carbamyl phosphate synthetase). (b) Findings Alkalosis without acetonuria andDNPH negative. Ammonia raised, lactate normal or raisedwithnormalblood glucose. calcium and blood count. (c) Usual diagnoses Urea cycle defects. fatty acid oxidation defects (glutaric aciduriatype 11, carnitinepalmitoyltransferase I1 (longchainacyl-CoAdehydrogenase,3-hydroxylong-chain acyl-CoA dehydrogenase).

6. Severe hypotonia, myoclonicjerks, seizures (a) Principal investigations Aminoacidchromatography, CSF amino acids, plasma phytanic acid and plasma very long-chainfatty acids. (b) Findings No acidosis, acetonuria and DNPH negative. Ammonia, lactate, glucose, blood count all normal. (c) Usual diagnoses N W , sulphiteoxidase,xanthineoxidase,peroxisomal disorders, pyridoxine dependency, trifunctional enzyme.

Hepatomegaly with deranged liver function

1. Hepatomegalyandhypoglycclemia (a) Principal investigations Fasting and loading tests. Liver, fibroblast and lymphocyte enzyme studies. (b) Findings Acetonuria with acidosis. Ammonia normal, lactate raised, moderate hypoglycaemia and normal blood count. (c) m i c a 1 diagnoses Fructosediphosphatasedeficiency,glycogenosistype I (acetest negative), glycogenosis type I11 (moderate acetonuria).

162 IMD - RECOGNIZABLE PATTERNS

2. Hepatomegaly, jaundice, liver failure and hepatocellular necrosis (a) Principal investigations Enzymestudies to excludegalactosaemia.fructosaemia and tyrosinaemia. Urinary organic acids. (b) Findings Slight acidosis and acetonuria. Ammonia normal or raised, lactate significantly raised and glucose normal or decreased. (c) Typical diagnoses Galactosaemia, fructosaemia, tyrosinosis type I.neonatal haemochromatosis, respiratory chain disorders.

3. Hepatomegaly, cholestatic jaundice, chronic diarrhoea and failure tothrive (a) Principal investigations Plasmaandurineorganic acids, proteinelectrophoresis, phytanic acid, very long-chain fatty acids, pipecolic acid and phytanic acid. (b)Findings Acidosis and ketosisare absent with normal glucose, lactate and ammonia. (c) Typical diagnoses a,-anti-trypsindeficiency,peroxisomaldisorders,inborn errors of bile acid metabolism.

4. Hepatosplenomegaly, storage signs, chronic diarrhoea and failure tothrive (a) Principal investigations Enzyme studies, mucopolysaccharides, sialic acidand oligosaccharides. (b)Findings Acidosisandketosisareabsent.Ammoniaandglucose normal with normal or raised lactate. (c) npical diagnoses Storage disorders, GM, gangliosidosis, infantile sialic acid storage disease (sialidosis U), I-cell disease, mucopolysaccharidosis type VII.

Further reading Chaves-Caballo E. Detection of inheritedneurometabolicdisorders:a practical clinical approach. Pediatric Clinicsof North America, 1992; 39: 801. Lyon G, Adams RD,Kolodny EH.Neurology of Hereditary Metabolic Diseasesof Children, 2nd edn. NewYork McGraw-Hill, 1996. Saudubray JM, Ogier H, Charpentier C. Clinical approach to inherited metabolic diseases. In: Femandes J,Saudubray J-M, Van den Berghe G (eds). Inborn Metabolic Disease: Diagnosis and Treatment,2nd edn. New York: Springer-Verlag, 1995; 3-39.

IMD

- RECOGNIZABLE PATTERNS 163

Schaub J, Van Hoof F, Vis HL (eds). Inborn Errorsof Metabolism (Nest16 Nutrition Workshop Series, Vol. 24). New York: Raven Press, 1991. Scriver CR, Beaudet Sly WS. Vale D (eds). The Metabolic and MolecularBasis of Inherited Disease,7th edn. NewYork: McGraw-Hill. 1995.

AL.

Related topics of interest Acute collapse (p.6) Death of a baby (p.72) Inherited metabolic disease- investigation and management (p. 156) Prenatal diagnosis (p. 253)

164 IMD

- RECOGNIZABLE PAlTERNS

INTRAUTERINE GROWTH RESTRICTION The provision of adequate nutrition for the growing fetus is essential for its normal development and has implications for future health and wellbeing during childhood and adulthood. IUGR is largely a consequence of fetal malnutrition. It is well known that the lighter a newborn infant is at birth the more likely it is tobecome ill or die. Recently, convincing evidence has accumulated linking fetal malnutrition with an increased morbidity and mortality from cardiovascular disease in adulthood.

Pathophysiology

Most fetuses, including those in multiple gestations, follow similar growth curves during the first 20 weeks of pregnancy with any slowing of growth usually onlyoccumng in the second half of pregnancy. Where the cause is physiological (e.g. multiple pregnancy or inherited genetic factors), slow growth is confined to the third trimester. The more severe the pathology, the earlier fetal growth restriction becomes evident. The earliest slowing of growth (during the second trimester) occurs when the fetus isinherently abnormal (e.g. congenitalor chromosomal anomaly) or has sustained significant first trimester insult (e.g. from intrauterine infection or drug exposure). Recentstudieshavegivenconsiderable insight into the pathophysiology of IUGR. At the start of gestation, growth appears to be controlled bynutritional input and growthfactors acting locally by autocrine and paracrine mechanisms. Among these, insulin-like growth factors (IGFs, especially IGF-I) and their binding proteins (IGFBPs) appearto have a central regulatory role. FetusesshowingIUGRhavelow IGF-l and IGFBP-3 levels butelevatedgrowthhormone(GH)levels. Following birth and renutrition, a rapid increase in IGF-l and a decrease in GH levels is observed. Thus GH, though playing a role in fetal and infantile growth, appears not to be the key hormone for fetal growth. On theother hand, insulin appears to play a major role in the regulation of fetal growth and it may exert this by increasing IGF-I production.

Definition

Newborn infants may be described according to their birthweight for gestation as appropriate for gestational age (AGA), small for gestational age (SGA) or large for gestational age (LGA). The definition of SGA varies from a birthweight below the 10th centile to one of less than the 3rd centile. In the UK, just over 2% of all babies maybe SGA, whereasin some developing nations, up to one in three newborns may be SGA and every other infant may be of low birthweight (LBW) (weighing IO days at term, >l4 days in preterm infants).

The 97th centile for bilirubin concentration in the first few days of life in the well, breast-fed term baby is approximately 250pmoM, and 2lOpmoM in theformula-fedbaby. These thresholds of concentration and time may therefore be taken as levels above which jaundice should be investigated for potentially pathological causes. Theyare not thresholdsfor initiating treatment, nor are they thresholds below which pathological causes for jaundice are absent. Vigilance is always needed.

1. Investigutiuns. A bilirubin concentration. blood group and Coombs’ test are the initial investigations in a well term baby who clinically looks jaundiced enoughto need treatment. Further tests are not indicated unless the need for treatment is confirmed by a high bilirubin concentration without evidence of haemolyticdisease.Tests on treated infants shouldinclude urine culture, urine reducing sugars (to exclude galactosuria, which tests positive onClinitest, but negative onClinistix), and further estimates of total bilirubin concentration. Liver function tests and conjugatedunconjugated bilirubin assays maybe needed to exclude hepatitis andconjugatedhyperbilirubinaemia, respectively,and certainly if the jaundice is prolonged. Some specific hepatic causes of jaundice are discussed in the topic‘Liver disorders’. Worldwide, G6PD deficiency is the

JAUNDICE 173

most important cause of jaundice, especially insouth-east Asia and African countries. In the UK, it is justifiable toscreen jaundiced male infants who are of an ethnic origin that has a high prevalence of G6PD deficiency.

2. Management. Generally, if thebaby is welland feeding well and if the concentration of bilirubin is below thetreatment level, no further action should be taken unless the jaundice deepens or becomes prolonged. If the bilirubin concentration is above the treatment threshold and likely to rise to a point where kernicterus is a risk, phototherapy is needed (see Table 1). Kernicterus is a pathological term meaning ‘yellow nuclei’, referring to theappearance of the basal ganglia when the brain is examined at post-mortem: the ganglia are stained because the fat-soluble unconjugated bilirubin has entered thebrain cells. Long-term neurological sequelae of this include deafnessandathetoidcerebralpalsy. Untreated severe hyperbilirubinaemia can cause fits, opisthotonus and death in the neonate. There iscontinuing debate about the threshold above which kernicterus is likely to occur. Recent work suggests that in well term infants without haemolytic disease (including G6PD deficiency) it is higher than originally thought. The term ‘vigintiphobia’ (fear of thefigure twenty) was coined to retlect paediatricians’ fear of the total bilirubin concentration rising above 20mg/dl (342pmolfl) lest kernicterus ensued. Now, a gentler approach to jaundice is used. and kernicterusis considered to be a significant risk only above a bilirubin concentration of 450pmolA in this group of infants. The setting of this value also setsthe level (450 pmoM) at which exchange transfusion to prevent kernicterus is mandatory. In turn, phototherapy is started when the bilirubin concentration is 100pmoIfl below this exchange line. In well term infants, therefore, phototherapy is startedatbilirubin concentrations as low as 80 pmolfl on day 1, rising to 350pmoM on day 3 and later. In summary, theapproach to jaundicein a well term babyis cascaded; starting with an examination to confirm the baby is well. If the baby looks significantly jaundiced, a single setof blood tests is performed. If treatment is indicated, phototherapy is started. This can be regarded as a treatment to avoid exchange transfusion. This in turn is the definitivetreatment to prevent kernicterus. Neither phototherapy nor exchange transfusions areharmless, and should be initiated only if necessary. There is, however, a greater risk of kernicterus at lower concentrations of bilirubin if the baby is preterm, has haemolytic disease, G6PD deficiency, hypoalbuminaemia, acidosis or is receiving any drugs that may displace bilirubin from the albu-

174 JAUNDICE

min binding sites. The thresholds for action have therefore to be reduced accordingly.

Preterm infants

There are insufficient coherent data on jaundice in pretem infants below 35 weeksgestation to develop scientific evidence-based guidelines about phototherapy. Table l contains some publishedrecommendationsandsomeextrapolations from them.

Prolonged jaundice

Jaundice is prolonged ifit lasts >l0 days in the term infant, and >l4 days in the preterm. The most common cause for this is breast milk jaundice in a well and thriving baby who has an unconjugated hyperbilirubinaemia secondary to an increased enterohepatic circulation. Unfortunatelythere is no specific ‘test’ for this, and it is always a diagnosis of exclusion after other more sinister diagnoses,including biliary atresia, are ruled out. Investigation starts with the question: is the hyperbilirubinaemia unconjugated or conjugated? If unconjuguted, first check: 0

0 0

Liverfunction. Thyroidfunction. Urine culture. Haemoglobinandred cell morphology.

If these are negative and the baby is a well, thriving and breast-fed, it is safe to watch for a further 2-3 weeks during which time thejaundice should fade and the baby remain well. If this does not happen, then more extensive investigations into causes of haemolysis, repeat liver function tests and specific conditionssuch as Gilbert’s andCrigler-Najjarsyndromes should be performed. If conjugated, it is pathological: there is a need for prompt diagnosis andreferral to a specialist centre at the outsetis often the best wayto achieve this. Among the important diagnoses to be considered and excluded are:

0

Biliary atresia. Neonatal hepatitis. a,-anti-trypsin deficiency. Inspissated bile syndrome. Dubin-JohnsonandRotorsyndromes. Choledocal cyst. CF.

JAUNDICE 175

Table 1. Guidelines for jaundice therapy (PrnoM) for phototherapy

Gestation Postnatal bilirubin and agelevel 1-2 c1 day

days

days 2-3 >3days _____

527 weeks orc1OOOg 28-32 weeks 32-35 weeks 237 weeks

85

100

85-120

100-150

100-1 50

150-200

85-170

170-260

100-150 125-175 220 260-350

150-175

175 220 >350

Further reading Dodd K. Neonatal jaundice - a lighter touch. Archives of Disease in Childhood, 1993; 68: 529-32. Maisels MJ. Neonatal jaundice. In: Sinclair JC, Bracken MB (eds). EIfectiveCare of the Newborn Infant. Oxford: Oxford University Press, 1992; 507-58. Maisels MJ. Newman TB. Jaundice in full-term and near-term infants who leave the hospital within 36 hours: the pediatrician’s nemesis. CIinics in Perinatology, 1998; 25: 295-302. Modi N. Jaundice. In: Harvey D, CookeRWI,LevittGA (eds). The BabyUnder 1OOOg. London: Butterworth, 1989; 120-33. Newman TB, Maisels MJ. Evaluation and treatment jaundice of in the term newborn: a kinder, gentler approach. Pediatrics. 1992; 89: 809-18. Seidman DS. Gale R, Stevenson DK. What should we do about jaundice? In: Hansen T N , McIntosh N (eds). Current Topics in Neonatology, No. 2. London: W.B. Saunders, 1997; 125-41. Volpe JJ. Bilirubin and brain injury. In: Neurology of the Newborn,3rd edn. Philadelphia:W.B. Saunders. 1995; 490-513. Watchko JF, Oski FA. Bilirubin=20 mg/dl=vigintiphobia. Pediatrics, 1983; 71: 660-3.

Related topics of interest Birth injuries (p. 21) Infants of diabetic mothers (p. 136) Liver disorders (p. 178) Polycythaemia (p. 241) Postnatalexamination(p.244)

176 JAUNDICE

Jitteriness is a fine rhythmic 5-6 Hz tremorof the arms and legs. It is the most common involuntary movement in newborn babies. In the majority of jittery babies there is no associated pathology.

Aetiology

0 0 0 0

0 0 0

Idiopathic. Hypoglycaemia. Hypocalcaemia. Drugwithdrawal. Prematurity. Intrauterinegrowth restriction. Infants of diabetic mothers.

Differential diagnosis

The challenge is to distinguish ‘jitters’ fromfits. The main feature is that jitteriness stops when the limb is held or gently restrained, whereas fits continue. Also there are no abnormal eye movements, and jitters can be provoked by stretching and then releasing a limb in contrast to the spontaneous onset of fits.

Management

Hypoglycaemiaandhypocalcaemiamustbeexcluded or treated if necessary. While hypocalcaemiais benign, jitteriness of hypoglycaemia maybe a heralding sign of a more profound hypoglycaemia with more Severe symptoms. Jitteriness as part of a drug withdrawal syndrome in a neonateoccurs after marijuana, caffeine and opiate drugwithdrawal, and has also been reported in infants of mothers on selective serotonin re-uptake inhibitors. Inthese situations, theoverall state of thebaby determinestherapy,ratherthanany one sign. Jitteriness in other babies is thought to be due to an immaturity of the nervous system, probably a lack of myelination. Up to 44% of well term babies were observedto be jittery in one series. For these babies, no treatment is needed. Jitteriness can continue into infancy, and again is benign.

Further reading Parker S, Zuckerman B, Bauchner H et al. Jitteriness in full-term neonates: prevalence and correlates. Pediatrics, 1990; 85: 17-23. Rennie JM (ed). Textbook of Neonatology, 3rd edn. Edinburgh: Churchill Livingstone, 1998. Taeusch H W , Ballard RA (eds). Avery’s Diseusesofthe Newborn, 7th edn. Philadelphia: W.B. Saunders, 1998.

Related topics of interest Intrauterine growth restriction (p. 165) Maternal drug abuse (p. 182)

Posmatal examination (p. 244) Seizures (p. 294)

JITTERINESS 177

LIVER DISORDERS Liver disorders commonly present with jaundice, abnormal liver function tests, or hepatomegaly and,less commonly, presentas part of a metabolic disorderor are discovered in the context ofother investigations.While the individual disorders may be quite rare, as a group these disorders are fairly common. However, the complete evaluation of some of these disorders can be technically difficult, and early referral to a specialist paediatric hepatology centre isdesirable when the diagnosis remains uncertain after a detailed history and examination complemented by the appropriate laboratoryinvestigations.

Biliary atresia

This i scongenital a condition occumng in 1 in 14000 babies in the UK. Bile cannot reach the intestine as the extra-hepatic ducts are blocked.Leftuntreated. 95% ofbabies die by 2 years of age. Treatment is by the Kasai operation - a porte enterostomy - in which the lower surface ofthe liver. stripped of its capsule, is applied to an open segmentof bowel to allow drainage of the bile. The earlier theoperation is done,the better. Success rates of >75% are achieved with surgery before 2 months in specialized units; after that it is only 25%. Liver transplantation after failed Kasai surgery is the final option. Earlyandpromptdiagnosis is needed: biliary atresia is alwaysthefirstdiagnosis to excludeinprolongedneonatal jaundice, even if it is mild. It is a conjugated hyperbilirubinaemia that can be confirmed by appropriate blood tests and the detection ofbilirubin in theurine, which is yellow, whereas the stools are pale. Differential diagnoses include intrahepatic biliary atresias. neonatal hepatitis, a,-anti-trypsin (A,AT) deficiency, choledocal cysts, CF, inspissated bile syndrome, and other rare metabolic or anatomical abnormalities. The complicated and urgent nature of this condition means that babies witha persistent conjugatedhyperbilirubinaemiashould be assessed at a specialist unit. Usually, onceother disorders have been excluded, the differential diagnosis lies between a neonatal hepatitis and biliary atresia. A technetium diisopropyl iminodiacetic acid (DISIDA) scan is performed to outline the biliary tree and detect bile excretion. The definitive diagnosis may be made only by open liver biopsy during an explorative laparotomy.

Neonatal hepatitis

Many use this as an umbrella term. but it is best to think of:

1. Infective hepatitis. 2. Cholestasissecondary cause.

to ametabolicdisease

or other

I . Infective heputifis. To make this diagnosis the baby must have symptoms consistent with infection and aminotransferase levels of >2.5 times the upper limit of normal in the absenceof 178 LIVER DISORDERS

other liver disease. Hepatitis viruses A, B. C, and D have all beenimplicated.Othernon-hepatitisvirusescanalso cause neonatal hepatitis, (e.g. rubella, CMV). (a) Hepatitis A Fetal transmission has not been demonstrated. Maternal peripartum hepatitis A is a threat to the baby as the virus spreads bycontactwithmaternalbloodandthefaecal-oralroute. Infants of mothers who develop hepatitis A within 2 weeks of delivery should receive0.5 m1 of immunoglobulin. (b) Hepatitis B Transmission to the baby is primarily from exposure to maternalblood at delivery.thoughmaternal-fetaltransmission is reported from Taiwan. Babies at high risk of transmissionarethosewhose mothers: 0 0

Have had hepatitis R in the last trimester. Are from south-east Asiaor from Afro-Caribbean countries. AreHBeAg positive.

As transmission occurs at birth, prevention is possible, and all babies of HbsAg-positive mothers should be vaccinated. Low-risk babies should receive a course of vaccine starting within 48 hours of birth. High-risk babies should receive vaccine and HBIG. In order toachieve this, screening of maternal hepatitis status during pregnancyis needed. This is not yet universal in the UK. Spread by the faecahral route is also possible andappropriateprecautionsshouldbetaken.Health workersshouldbevaccinatedandshown to beimmune. Infected babies can go on to have a transient disturbance of liver enzymes, acute hepatitis that, in its worst form. can be fulminant and fatal, or a chronic hepatitis leading to cirrhosis. See ‘Hepatitis B’.

2. Cholesrasis. Cholestasis (‘hepatitis’) secondary to a metabolic disease or other cause including: (a) Metabolic 0 A,AT deficiency. 0 CF. 0 vrosinaemia. 0 Galactosaemia. 0 Fructose intolerance. 0 Lipidstorage disorders. 0 Peroxisomal disorders. Haemochromatosis. Hypothyroidism. 0 Hypopituitarism.

LIVER DISORDERS 179

(b) Other 0 Down'ssyndrome. Parenteral nutrition. 0 Familial cholestatic syndromes. Of these, galactosaemia is immediately life-threatening and presents with asepsis-like picture several days afterstarting to ingest milk (lactose). Bedside testing of the urine for a reducing sugar that is not glucose (positive Clinitest, negative Clinistix (Ames Laboratories, UK)) in such a jaundiced baby is mandatory.All feeds are stopped and i.v. glucose started if galactosaemia is suspected. The hepatitis resolveswitha lactose-free intake - initially the i.v. glucose, then a special diet for life. The diagnosis is confirmed by assaying red cell galactose-l-phosphate uridyl transferase. There are many genetic variations of A,AT deficiency. Its principal function is the inhibition of neutrophil elastase, and when deficient, neutrophil-mediated inflammation can progress in the liver and lungs. When it is suspected, phenotype testing is undertaken: measurement of A,AT itself can be misleading in the presence ofhepatitis. The normal phenotype is the so-called PiMM (Pi - protease inhibitor), and the one most commonly associated with neonatal liver disease is Pm. There is geographical variation in the frequency of the genes: in the UK, southern Europe and the USA, about 1 in 3000 babies is born with PiZZ. Tenper cent of such infants develop cholestasis in infancy, though 50% may have abnormal liver function tests by the end of thefirst year. A,AT deficiency must be excluded in cases of late haemorrhagic disease of the newborn. Most with cholestasis progress relentlessly to cirrhosis and liver failure. Treatment is supportive until transplantation is necessary.

Specificdisorders of bile metabolism

" k o steps in theconversionofunconjugated

bilirubin to a conjugated water-soluble form involve uridine diphosphate glucuronyl transferase (UDPGT) which converts bilirubin to bilirubin monoglucuronide and is also capable of converting that to the diglucuronide. Bilirubin monoglucuronide dismutase catalyses the conversion to the diglucuronide.

I. Syndromes with UDPGT deficiency (a) Crigler-Najjar syndrome (type 1) Autosomal recessive. 0 Complete absence of hepatic glucuronyl transferase. 0 Persistent unconjugated hyperbilirubinaemia, usually >340pmolil. 0 Kernicterusininfancy. Death in infancy, some surviving to adulthood then developing kernicterus.

180 LIVER DISORDERS

Treatment - phototherapy. Transplantation - prior to neurological complications. Phenobarbitonehas no effect. (b) Crigler-Najjar syndrome (type 2) Autosomalrecessive/dominant(variablepenetrance). Less severe persistent unconjugatedhyperbilirubinaemia. Treatment with enzyme-inducing phenobarbitone and phototherapy reduces bilirubin levels. Neurologicalproblemsunusual. (c) Gilbert's syndrome Autosomaldominant. Affects 5% of the population. Benign,mild,chronicunconjugatedhyperbilirubinaemia. Bilirubin clearance about one-third of normal. Impaired UDPGT activity and impaired hepatic uptake. 50% of cases have reduced red-cell survival. 0 Bilirubin rises with fasting, exercise. intercurrent illnesses. 0 Rarelyrecognizedbeforepuberty. 0 Phenobarbitonereducesjaundice. (d) Dubin-Johnson syndrome 0 Autosomal recessive. Chronicconjugatedhyperbilirubinaemia. Jaundice may be seen after birth, but may not appear until fourth decade. Diagnosis by exclusion of other causesofconjugated hyperbilirubinaemia and bytypical liver biopsy appearance of deposition of melanin-like pigment. 0 No treatmentnecessary. (e) Rotor's syndrome 0 Autosomal recessive. 0 Predominantlyconjugatedhyperbilirubinaemia. 0 Benign.

Further reading Altschuler SM, Liacouras CA. Pediatric Gastroenterology and Liver Disease. Edinburgh: Churchill Livingstone, 1998. Mowat AP. Liver Disorders i n Childhood, 3rd edn. Oxford: Butterworth Heinemann, 1994.

Related topics of interest Inherited metabolic disease - investigation and management (p. 156) Jaundice (p. 173)

LIVER DISORDERS 181

Drug addiction during pregnancy has deleteriouseffects on the mother, herfetus, the immediate family and the rest of society. A high proportion of drug-abusing women are in relationships with men who also abuse drugs with up to two-thirds having been subjectedto physical and sexual abuse. Mental health problems are frequentamong drug-abusing individuals. Selfcare and diet therefore tend to be neglected with consequential fetal compromise. Drug abuse is on the increase particularly in the developed nations though prevalencerates vary widely, being highest (up to 15%) in inner-city areas. It is not only confinedto women of low socioeconomic status but occurs in all social groups regardless of income level or ethnichcial identity. Mood-altering drugs are often used along with alcohol with a tendencyfor the younger agegroup (under 30s) to use two or more drugs. Of theinfants diagnosed as having A D S in the UK in 1996, outside London, approximately threequarters of the mothers or their partners contracted HIV infection through i.v. drug abuse.

Indicators of possible drug abuseinpregnancy

1. Medical Self admission of use. 0 Sporadic or no prenatal care before delivery. 0 Preterm labour and deliveryor abruptio placenta. 0 Stillbirth or birth of infant with anomalies.

2. Social 0 Frequent changes of residenceor employment. 0 Past drug or alcohol abuse. 0 Imprisonment. 0 Family violence. 0 Removal of other children from the home. 0 A disruptive or dysfunctional lifestyle.

Commonlyabused drugs 0 0 0 0 0

0 0

Management during pregnancy

Alcohol (fetal alcohol syndrome). Cocaine (microcephaly, cardiac malformations). Amphetamines. Marijuana. Cannabis. Heroin. Codeine. Barbiturates.

Encourage the mother to enter an alcohol and drug treatment programme, often in conjunction with a psychiatrist specializing in drug and substance abuse. Mothers addictedto narcotics may be switched to methadone (decreased risk of infection) whichcan be graduallyweaned.Methadone,however,has more prolonged and severe withdrawaleffects. Mothersshould be screened for possible hepatitis R and HIV infection following appropriate counselling. Social services should be involved with the appointmentof a key worker with arrangements for long-term follow-up.

182 MATERNAL DRUG ABUSE

Neonatal presentationof maternal drug abuse

Most infants will present with symptoms of drug withdrawal. These are not drug-specific but the timing of withdrawal symptoms is characteristic with some drugs. Opiate withdrawal (e.g. heroin) has a rapid onset (maximum intensity on day 2-4 and fading by 10-14 days) whereas methadone withdrawalpersists overweeks or months.Withdrawalsymptomsmayresolve withinafew days or persist for severalweeks,whilethe growth impairment and neuro-behavioural effects may last for several months.

Symptoms of withdrawal syndrome

1. Central nervous system Restlessness. Imtability. Tremulousness. Hyperactivity (with rub marks). High-pitched cry. Hyperacusis. Hypertonus. Yawning. Photophobia. Seizures. 2. Respiratory system Tachypnoea. Stuffy nose. Rhinorrhoea. Sneezing. Hiccups. Apnoeas. Respiratory distress. 3. Gastrointestinal system Salivation. Vomiting. Diarrhoea. Poor feeding. Poor weight gain.

Management of the infant 1. Acute Aim to promote normal sleep patterns. Nurse in quiet environment. Monitorbloodglucoseespecially in lowbirthweight infants with feeding difficulties. Firm wrapping reduces irritability and hyperactivity. For severe irritability with feeding difficulties, give chlopromazine (1-3 mgkglday at 3-6-hourly intervals) or opiates titrating against symptoms. Prophylactic therapyis not appropriate - only treat if symptomatic. The use of 'score charts'. comprising a record of withdrawalsigns and symptomsagainsttime,providesan MATERNAL DRUG ABUSE 183

0

objective assessment of the infant's clinical status and can guide treatment. Treat seizures with phenobarbitone, phenytoin, clonazepam or paraldehyde. Taper drug therapy gradually (over weeks to months). Breast-feeding is contraindicated.

2. Long-tenn. Assess social circumstanceswith social services to decide whether the child can be allowed home and decide on long-termfollow-up.Infantswith fetal alcohol syndrome require appropriate neurodevelopmental follow-up. Neurodevelopmental outcome maybe suboptimal, particularly in infants born to mothers abusing alcohol and cocaine and those brought up in families with disruptive or dysfunctional lifestyles.

Further reading Clinics in Perinatologv, 1991; 18: 1-191. Chasnoff IJ, Scholl SH. Consequences of cocaine andother druguse in pregnancy. In: Washton A, GoldMS (eds). Cocaine: A Clinicians Handbook.New York: Guildford Press, 1987; 241. Durand DJ. Espinoza AM. NickersonBG. Association between prenatal cocaine exposure and sudden infant death syndrome. Journal of Pediatrics, 1990; 117: 909. Fetters L. Tronick EZ.Neuromotor development of cocaine-exposed and control infants from birth through 15 months: poor and poorer performance. Pediatrics, 1996; 98: 938-43. Finnegan LP. Perinatal substanceabuse:commentsandperspectives. Seminars in Perinutolog?, 1991; 15: 331. Harrison M. Drug addiction in pregnancy: theinterface of science, emotion andsocial policy. Journal of Subsrance Abuse and Treatment,1991; 8: 261. Nicoll A. McGarrigle C. BradyT et al. Epidemiology and detection of HIV-I among pregnant women in the UnitedKingdom: results fromnationalsurveillance 1988-1996. British Medical Journal, 1998: 316: 253-8. Niebyl JR.Drug Use in Pregnancy, 2nd edn. Philadelphia: Lea & Febiger, 1988. ShawNJ,McIvor L. Neonatalabstinencesyndrome after maternalmethadonetreatment. Archives of Disease in Childhood, 1994; 71: F203-5.

Chasnoff IJ (ed). Chemical dependency and pregnancy.

Related topicsof interest HIV and AIDS (p. 114) Infection - perinatal (p. 147) Intrauterine growth restriction (p. 165) Seizures (p. 294)

184 MATERNAL DRUG ABUSE

MECHANICAL VENTILATION Mechanical ventilation using positive airway pressure is indicated for babies with respiratory failure secondary to lung or cardiac disease, for some with recurrent apnoeas or fits, and during deep sedation or anaesthesia. The ventilators used are traditionally time-cycled. pressurelimitedventilators,i.e.thetime oftheinspiratoryand expiratory phases are set.andthe ventilator deliverscertain preset pressures. Such ventilators have beenadapted for trigger ventilation. HFOV, volume-controlled ventilation and liquid ventilation are also used. In severe respiratory failure with ventilation-perfusion mismatch, NO may be introduced into the inspiratory gases to dilate the pulmonary vasculature and ECMO may be used in near-term infants with severe respiratory failure.

Continuous positive airwaypressure (CPAP)

CPAP is an attempt to mimic the positive-end expiratory pressure a baby generates by grunting during expiration against a closed glottis. The generated positive pressure reduces atelectasis. CPAP can be administered by face mask, endotracheal tube or nasal prongs. Increasingly it is applied by short, soft nasal prongs on the end of a CPAP driver circuit. These devices sense airway pressure changes secondary to the baby's spontaneous respiratory effort and alter gas flowsto maintain a near constant airway pressure. This may reduce the workofbreathing. A comparison of neonatal outcomes in American units showed that the unitusing early CPAP and toleratingslightly higher PaCO,hadthelowest incidence of chronic lung disease. At the same time, reports from Scandinaviausing similar techniques suggested benefits of early CPAP,and this modality of treatment is currently being reexplored. Preterm babies extubated during recovery from respiratory distress onto nasal CPAP are less likely to need reintubation than those extubated into a headbox. CPAP is also an important treatment of obstructive and mixed apnoeas, in which the soft structures of the upper airway may collapse inwards during the baby's negative pressure inspirations. CPAP 'splints' open the airway.

Intermittent positive pressureventilation (IPPV)

In IPPV, the inspiratory and expiratory pressures, inspired oxygenfraction(FiO,),inspiratory time (Ti), expiratory time (Te) and hence the rate (bpm) and the T i e ratio can all be controlled.

1. Target ranges for blood gases pH - arterial pH should preferably be 27.25 (17.3 in the first week of life). 0 Pa02 - the recommended range is 6-lO.kPa. PaCO, - this should be 25 kPa. If the pH is >7.25, there may be an advantage in letting the PaCOz rise towards7.5 kPa in the hope of avoiding baro- and volutrauma. There is

MECHANICAL VENTILATION 185

increasing evidence linkingearly hypocapnia withan increased incidence of BPD and PVL. SaO, - a range of 90-9595 is best, but arterial gases are needed to confirm adequate oxygenation and pH.

2. Arterial Oxygenation (PaO,). This can be controlled by: Changing theFiO,. Changing the mean airway pressure by: Changing the peak inspiratory pressure (PIP). Changing the PEEP. Changing the Time ratio. Lengthening the inspiratory plateau (increasing inspiratory gas flows). As PaO, varies directly with mean airway pressure (MAP) between 5 and 15cmH,O, increasing MAP will improve oxygenation.

3. Arterial carbon dioxide tension (PaCO,). This varies inversely with minute volume, the product of rate and stroke (tidal) volume, which is 5-8 mlkg in conventionally ventilated babies. Thus PaCO, can be controlled by: Changing therate. Changing the tidal volume by: Changing the PIP. Changing the PEEP (likely to have the for the same degree of change).

greater effect

Remember that CO, retention can be caused by inadvertent PEEP (PEEP higher than set) duringhigh-rate ventilation with short expiratory times. Acute unexpected rises in PaCOz often indicate an endotracheal tube blockage or pneumothorax.

Synchrony between the baby and theventilator

In IPPV, the ventilator and the baby may breathe independently of one another, causing inefficientventilation,variabletidal volumes and high intrapulmonary pressures that result in an increased incidence of pneumothoraces. The ventilator-baby interaction should be studied to ensure that the babyis breathing synchronously. This is achieved by the following:

I . Capturing the baby’srespiration. This is done by increasing the ventilator rate to just above the baby’s spontaneous rate (often 80 bpm or more in babies 1200g has been reported, and it is also uncertain whether the technique can be applied to the more difficultpopulation of babies d 5 0 g .

Further reading Avery ME, Tooley W, Keller JB et al. Is chronic lung diseasein low birthweight infants preventable? A survey of eight centers. Pediatrics, 1987; 79: 26-35. Bancalari E, Sinclair JC. Mechanical ventilation. In: Sinclair JC, Bracken MB (eds). Ffecrive Care of the Newborn Infant. Oxford Oxford University Press, 1992; 200. Goldsmith JP, Karotkin EH (eds). Assisted Ventilation of rhe Neonate, 3rd edn. Philadelphia: W.B. Saunders, 1996; 215-28. Goldsmith JP, Spitzer AR (4s). Controversies in neonatal pulmonary care. Clinics in ferinatology, 1998; 25 (1).

Related topics of interest Complications of mechanical ventilation (p. 54) Intubation (p. 170) Pulmonary air leaks(p. 256) Respiratory distress syndrome (p. 278) Sedation and analgesia on the neonatal intensive care unit (p. 291)

188 MECHANICAL VENTILATION

MECONIUM ASPIRATION SYNDROME This life-threatening condition occurs with increasing frequency as gestation advances. The incident of MAS varies in different parts of the world ranging from 1 to 5 per IO00 births. Higher rates are reported from North America and the Middle East compared to Europe. Though up to 15% of all deliveries may be complicated by meconium staining of amniotic fluid, only 5-10% of babies born through meconium-stained liquor develop pulmonary disease. In utero passage of meconium is uncommon because of the good anal sphincter tone, lack of strongintestinal peristalsis and the meconium normally plugging the rectum. Acidosis, asphyxia and compression of the fetal head all stimulate relaxation of the anal sphincter and intestinal peristalsis. Fetal hypercarbiaand hypoxia stimulate gasping which can lead to meconium aspiration. Passage of meconium before 34 weeks is rare but consider listeriosis (causes liquefaction of meconium) if it occurs.

Pathogenesis

Clinical features

Aspirated meconium reaches peripheral the airways, causing partial or complete obstruction. Partial obstruction causes gas trapping and lung over-distension (a ‘ball-valve’effect). Complete obstruction leads to atelectasis and ventilation-perfusion mismatch.Meconium inhibits surfactant action, the normal bacteriostatic qualities of amniotic fluid, and also produces a chemicalpneumonitis.Furthermore,hypoxia.acidosisand hypercarbiaproducepulmonaryvasoconstrictionleading to pulmonary hypertension, right-to-left shunting and worsening gas exchange. Fetal distress during labour. Post-term andor IUGR. Meconium staining of theskin, nails, umbilical cord. Hypoglycaemia. Metabolic acidosis. Cyanosis and hypoxaemia. Tachypnoea or gasping respiration. Pneumothorax (30% with severe MAS). Post-asphyxial signs (CNS, renal or cardiovascular). PPHN.

Diagnosis

This is based on thepresence of meconium-stained liquor, meconium below the cords or chest radiological appearances (lung over-inflation, widespread coarse, fluffy opacities, pneumothorax and pneumomediastinum).

Management

Admit all infants with meconium below the cordsfor observation. Symptomatic infants should have pulse oximetry, supplemental oxygen (as required), blood gas analysis and a chest X-ray.Commencebroad-spectrum antibiotics after cultures. Respiratory failure and severe hypoxaemia requires intubation andmechanical ventilation. Surfactantadministration, fast rates and low PEEP, high-frequency ventilation may improve

MECONIUM ASPIRATION SYNDROME 189

gas exchange. Inhaled NO (a selective pulmonary vasodilator) may further improve oxygenation when used in conjunction withconventional or high-frequency ventilation. Refractory hypoxaemia unresponsive to the above measures is an indication for ECMO. Asphyxiatedinfants with MAS may have multisystem involvement (e.g. renal failure, seizures, hypotension) which need specific therapy.

Prevention

Identify fetuses at risk of asphyxia (IUGR. post-term. oligohydramniotic) and monitor carefully during labour. A skilled neonatal resuscitator should attenddeliveries complicatedbymeconiumstainingofliquor. Clear mouthand pharynx when head is delivered, and following delivery view the larynx. If meconium is present aspirate carefully. If thick meconium is present or meconium is seen below the cords, aspirate the trachea using alarge-bre suction catheter or carefully intubate then repeatedly aspirate the trachea. Endotracheal tube adapters or other mechanical aspirators should be used to prevent the resuscitator from being contaminatedwithanyinfectiousagents(e.g. HIV) presentinthe amniotic and vaginal fluids. Although up to half of all meconium-stained infants may have meconium in their trachea, and 1 in 10 may have meconium below the cords despite it being absent from the mouth or pharynx,intubation of all meconium-stained infants is associated with a greater morbidity. Mild disease not requiring mechanical ventilation has an excellent prognosis with recovery within a few days. Recently, mortality fromsevereMAS has declinedfromalmost 50% to 4-18%. Most deaths are due to air leaks, PPHN, respiratory failure or associated perinatal asphyxia. There is an increased risk of asthma and exercise-induced bronchial reactivity in survivors. The use of hyperventilation-induced hypocapnia (PaCO, c25 mmHg or ~ 3 . 5kPa) in treating PPHN is associated with adverse neurodevelopmental outcome (e.g. sensorineural hearing loss and low psychomotor developmentaltest scores). Perinatal asphyxia is associated with a mortality and neurodevelopmental morbidity related to the severity of the asphyxial insult.

Further reading Cunningham AS, Lawson EE, Martin RJ et al. Tracheal suction and meconium: a proposed standard of care. Journal of Pediatrics, 1990; 138: 153. HalahakoonCN.HallidayHL.Otheracutelung disorders. In: Yu VYH (ed). UailliPres Clinical Paediatrics, Vol. 3. No. 1, Pulmonary Problems in the Perinatal Period and their Sequelae. London: Baillitre Tindall, 1995; 87-1 14.

190 MECONIUM ASPIRATION SYNDROME

Halliday HL.Other acute lungdisorders. In: Sinclair JC, Bracken MB (eds). Eflective Cureof the Newborn Infant. Oxford: Oxford University Press, 1992; 359-84. Spitzer AR (ed). Intensive Cureof the Fetus and Neonate.St. Louis: C.V.Mosby, 1996. Wiswell TE, Tuggle JM, Turner BS. Meconium aspiration syndrome: have we made adifference? Pediatrics, 1990; 85: 715-21.

Related topics of interest Bronchopulmonary dysplasia (p. 38) Extracorporeal membrane oxygenation (p. 78) Hypoxic-ischaemic encephalopathy (p. 128) Intrauterine growth restriction (p. 165) Intubation (p. 170) Mechanical ventilation (p. 185) Persistent pulmonary hypertension of the newborn (p.237) Respiratory distress (p. 275)

MECONIUM ASPIRATION SYNDROME 191

MULTIPLE PREGNANCY Multiple pregnancy rates vary worldwide. For instance, the prevalence of twin births varies from 6.7 per 1000 deliveries in Japan to 40 per lo00 deliveries in Nigeria. This is duelargely to variations in dizygotic twinning, as the prevalence of monozygotic twinning is relatively constant worldwide at 3.5 per l000 births. Dizygotic twins arise when two ova are released and fertilized in one menstrual cycle; monozygotic twins arise when one ovum is fertilized and the resulting zygote dividesinto two. Over the last two decades, the incidence of twins and higher order births ha.. been rising, partly due to the more widespread use of assisted reproductive techniques. However, multiple pregnancy is associated with greater risks for both mothers and fetuses compared with a singleton pregnancy. This is because every complication of pregnancy occurs more commonly. The most important complication of multiple pregnancy is preterm delivery, with its concomitant increased perinatal morbidity and mortality. Thus twins account for only 2% of births, but 9% of all perinatal deaths due to their prematurity and low birthweight. The perinatal mortality rate among higher order births is directly related to the number of fetuses. The average length of a twin pregnancy is 20 days shorter than a singleton one.The mean duration of pregnancy decreases as the number of fetuses in utero increases. Approximately 25% of twins are born preterm. The mean gestational age at delivery for triplets is 33 weeks (with 85-90% delivering before 37 weeks and 20-3070 before 32 weeks). Almost all quadruplets experience preterm delivery (half before 32 weeks gestation).

Maternal r i s k s associated with multiple pregnancy b

e e b

e e e e e b

Fetal risks associated with multiple pregnancy

e b

e b

e e

Increased symptoms of early pregnancy (e.g. nausea and vomiting). Increased risk of miscamage. The vanishing twin syndrome. Preterm labour and delivery. Hypertension (pre-eclampsia and eclampsia). Antepartum haemorrhage. Hydramnios (in up to 12% of multiple pregnancies). Possibleneed for prenatalhospitalization for prolonged periods. Antepartum fetal death (risk of DIC in up to 25%). Risk of operative delivery (increased risk of trauma and infection). Increased likelihood of Caesarean delivery. Post-partum haemorrhage. Postnatal problems (e.g. increasedrisk of depression). Stillbirth or neonataldeath (perinatal mortality rate of twins is up to 10 times that of singletons). &term labour and delivery (rates of 30-50%). IUGR (25-33% have birthweight 4 0 t h centile). Congenitalabnormalities(twice as commoncompared with singletons). W i n to twin transfusion. The 'stuck' twin phenomenon (occurs in 8% of twin pregnancies but mortality is >80% for both twins).

192 MULTIPLE PREGNANCY

0 0

0

0 0 0

Specific problems associated with multiple PwPa"cY

Hydramnios(malpresentation). Cord accidents (carry a perinatal mortality of up to 50%). Risk of asphyxia (mortality risk from aqphyxia for twins is four to five times that of a singleton). Operativevaginaldelivery. Deathofaco-twin. Twinentrapment (rare, typically occurs in monoamniotic twins, incidence of 1 in 800, high risk of fetal death).

1. Determining zygosity. Thisis ofimportance as monozygotic pregnancies have increased morbidity and mortality. Twins of different sex are obviously dizygotic. Monozygosity can be proven on the basis of a monochorionic placenta. However, monozygotic twins with dichorionic placentas may only be distinguished reliably fromlike-sexdizygotictwinsby blood grouping, redcell and tissue enzymes, serum proteinsor minisatellite DNA probe tests.

2. Fetal nutrition and growth. Multiple fetuses of necessity compete for nutrition. Fetal growth in twins is usually similar to that of singletons until approximately 24 weeks' gestation. Thereafter,bodyweight falls disproportionatelymorethan head growth. The average birthweight of a newborn twin is 500 g less than a singleton. Dichorionic twins are heavier than monochorionic twins.

3. Twin-twin transfusion syndrome.

'

Placental arteriovenousvascularanastomosescan result in thetwin-twin transfusion syndrome, usually in monozygotic monochorionic twins. A cord blood haemoglobin difference of at least 5 gldl is noted between the twins.An incidence of 5-15% of all twin pregnancies has been reported, and the acute severe twin-twin transfusion syndrome occurs in 1% of monochorionic gestations. The donor twin becomes anaemic, hypovolaemic, oligohydramniotic and growth-restricted. The recipient twin becomes polycythaemic, hypervolaemic, polyhydramniotic and may develop cardiac failure, ascites, and pleural and pericardial effusions. Hydrops fetalis may develop in both. Antenatal treatment includes laser ablation of anastomoses, repeated amniocentesis, transfusion of donor and exsanguination of recipient. Mortality may be high (80-100%) for twins presenting acutely at 18-26 weeks gestation.

4. 'Stuck' twin phenomenon. One fetus in adiamniotic pregnancy lies in a severely oligohydramniotic sac while the co-twin lies in a severely polyhydramniotic sac. Mortality is high (>go%). Most result from twin-twin transfusion syndrome.

5. Congenital anomalies. Major anomalies are twice as common in multiple pregnancies compared with singletons.

MULTIPLEPREGNANCY 193

Cardiac anomalies, bowelatresia, neural tube defects and chromosomal abnormalities are more common in multiple pregnancies. Certain malformations uniquely occur in monozygotictwins(namelyconjoinedtwins) (1 in 5OOOO pregnancies),thecommonestformbeingthoracopagusand acardia (1 in 30000-35000 deliveries).

6. Death of a co-min. Fetal demise of one twin occurs in 0.5-6.8% oftwinpregnancies after the first trimester. The emboli and debris from the dead fetus may enter the circulation of the surviving (monochorionic)twin, producing multiple brain, gastrointestinal and renal lesions. In contrast, surviving dichorionic twins have a good prognosis. Regardless of zygosity, malesfare less well than females and malc-malepairs have thehighest perinatal mortalityrates.Inmale-female pairs, female infants fare better. The second-borntwinmay be at greater risk of death and morbidity.

Further reading Fowler MG, Kleinman JC, Kiely JL, Kessel SS. Double jeopardy: twin infant mortalityin the United States, 1983 and 1984. American Journalof Obstetrics and Gynecology, 199l; 165:

15-22. Fusi L, McParland P, Fisk N, Nicolini U, Wigglesworth J. Acute twin-twin transfusion: a possiblemechanism for brain-damaged survivors after intrauterine deathofamonochorionic twin. Obstetrics and Gynecology, 1991; 78: 517-20. Hawrylyshyn PA, Barkin M, Bernstein A, Papsin FR. Twinpregnancies - acontinuing perinatal challenge. Obstetrics and Gynecology, 1982; 59: 463-6. Keith LG, PapiernikE, Keith DM, LukeR (eds). Multiple P regnancy. Epidemiology,Gestation and Perinatal Outcome. London: Pathernon Publishing Group, 1995. Little J, Bryan E. Congenital anomalies. In: MacGillivaryI, Campbell DM, Thompson B(eds). Twinning and Twins. Chichester: John Wiley, 1988; 207-40.

Related topicsof interest Congenital malformations and birth defects (p. 70) Intrauterine growth restriction (p. 165) Pregnancy complications and fetal health (p. 247) Prenatal diagnosis (p. 253)

194 MULTIPLE PREGNANCY

NECROTIZING ENTEROCOLITIS The first reported cases of NEC were made over 150 years ago, although the term NEC was first used in the 1950s. NEC is a maladaptive response of the immature gastrointestinal tract to perinatavpostnatal injury. Damage to the intestinal mucosa in the presence of intraluminal feeds and microbial infectionare important aetiological factors. Intestinal ischaemia, from any cause, rapid oral feeds, non-human milk formula and bacterial infection are thought to be particularly important. Abnormal prenatal umbilical wave forms (absent and reversed enddiastolic flow) and marked IUGR are particularly associated with NEC. Approximately 90% of cases occur in premature infants, with the incidence varying with gestational age from0.1 per IO00 live births in term infants to almost 8% in the very low birthweightinfants. It is most frequently seen within the first 2 weeks of life although it may occur in infants who are several weeks old. Approximately 300 cases occur annually in the UK with 70-100 deaths. Although the caecum, ascending colon and terminal ileum are the most commonly affected sites, any part of the gastrointestinal tract may be involved. The affected segment of gut may only show small perforationsor be severely affected and necrotic.

Clinical features

These are varied, from the non-specific signs hypotonia, of lethargy. and apnoeas with temperature instability, to the signs of septic shockwithhypotension,bradycardia,pallorwith abdominal distension, bloodystools, bilious aspirates and DIC. A silent tender abdomen with a red and indurated abdominal wall suggests a perforation.

Investigations

I . Radiology. Plain abdominal X-ray shows thickened dilated loops of bowel (which maybe fixed) occasionally with fluid levels. In the acute phase of the disease, daily radiographs should be performed. A lateral abdominal film (right side up for better air-liver contrast) is important in the acute stage of the disease, as perforations may be difficult to detect otherwise. Typical radiographs show intramural gas (pneumatosis intestinalis) and in later stages, air may also be seen in the liver, along withascites. Intra-abdominal abscesses andascites may be more readily recognized with ultrasound. 2. Haematology

mc.

Coagulationscreen.

3. Biochemistr?, U&E. 0

Blood gases.

4. Microbiology. Performa full septic screen(omit LP if diagnosis is clear).

Management

Stop oral feeds to rest the gut and commence parenteral nutrition for at least 10 days. Deflate the abdomen with a nasogastric tube on free drainage.Administer FFT intheacute

NECROTIZING ENTEROCOLITIS 195

phase of the diseaseat 10-20 mlkg depending on the clinical state (wide core-peripheral temperature gap, poor capillary refill, hypotension). Transfuse with packed red cells if anaemic. Support the blood pressure (keep mean arterial blood pressure 235 m H g ) with colloids and inotropes (dopamine 10-20 pglkglmin or dobutamine 10-30 pgilcg/min). Monitor arterial blood gases, correct acidosis and commence ventilation if hypoxic and retaining carbon dioxidein the presence of apnoeas. Carefully monitor electrolytes and hydration with 6-12-hourly electrolytes in theacute phase of the disease, then less frequently later when more stable. Control infection with i.v. broad-spectrum antibiotics including metronidazole. Correct DIC and transfuseplatelets if marked thrombocytopenia is present (platelet count c20 X 103/mm3).Provide adequate analgesia by infusing opiates (e.g. 10-4Opg morphine/ kghour). Treat intercurrent problems such aselectrolyte imbalance and hypoglycaemia promptly. Surgery is required when a perforation hasoccurred or when there iscontinuingdeterioration (with persistent acidosis) despite adequate medical treatment. In the unstable sick very low birthweight infant, simple drainage of the peritoneal cavity under local anaesthetic may be a useful interim measure until the infant is fit for surgery. Enteral feeds (preferably expressed breast milk or a simplified formula, e.g. Prejestimil-. Mead Johnson) may be recommenced slowly in the well infantafter 10-14 days (or longer if surgery was required). Relapses may occur in up to 10% of cases following re-introduction of enteral feeds.Complications include stricture formation with intestinal obstruction and short bowel syndrome following bowel resection.

Further reading Bauer CR. Necrotizing enterocolitis. In: Sinclair JC,Bracken ME (eds). E’eective Care of the Newborn Infant. Oxford: Oxford University Press, 1992; 602-16. Stoll BJ, Kliegman RM (eds). Necrotizing enterocolitis. Clinics in Perinafology, 1994; 21 (2).

Related topics of interest Abdominal distension (p. 1) Acute collapse (p. 6) Neonatal surgery (p. 200) Shock (p. 302) Surgical emergencies (p. 312) Vomiting (p. 331)

196 NECROTIZING ENTEROCOLITIS

NEONATAL SCREENING FOR INHERITED DISEASE Mass screening of newbornsfor metabolic disorders was introduced by Bob Guthrie (Guthrie test for phenylketonuria (PKU)) some three decades ago. Conditions which merit screening occur frequently, have gradual onset (allowing time for detection before the onset of s y m p toms) and canbe detected by inexpensive and accurate assays. Early treatment should produce a good outcome.This is ideal for PKU.

Phenylketonuria

PKU has an incidence of 1 in 12 OOO births and in the classic form is due tophenylalanine hydroxylase deficiency. However, tetrahydrobiopterin co-factor defects may also produce PKU. The PKUscreening test identifies all infants withelevated serumphenylalanine.Anaminoacidchromatogram is performed on a heel prick spot of blood collected onto filter paper. Other disorders canalso now be detected from this same blood sample including tyrosinaemia,MSUD as well as some genetic disorders (from DNA analysis). Infants with serum phenylalanine values persistently above 1.O mmolA (18 mg/dl) need treatment. Infants with phenylalanine levels of 0.2-0.6 mmoVl (4-10 mg/dl) on the first test should have a repeat test. Levels of 20.6 mmoVl (10 mg/dl) needfurtherassessmentandmayneedtreatment.Infants should be tested whenon full feeds(commonly days 4-6) and off i.v. fluids. Treatment should be carried out by those expert in this area. In essence, most of the amino acid requirements are provided in synthetic form and natural proteins only used in sufficient amounts to supply the phenylalanine requirements for growth, leaving no excess to be broken down to tyrosine.

Hypothyroidism

1 in 3500 births. Most Hypothyroidism has an incidence of screening programmes use a single blood sample takenat day 5-10 (when relative stability has returned to the thyroid axis after the abrupt changes at birth). A heel prick spot of blood is collected onto filter paper at the same time and onto the same paperas the PKUtest. Thyroxine screening aloneis inadequate because of the overlap between normal and hypothyroid values.Thyroid-stimulatinghormone(TSH)assay is the primary test performed (though this may miss the rarer cases of secondary hypothyroidism (pituitary or hypothalamic hypothyroidismwith an incidence of 1 in 60000-100000 births). Normal TSH levels are 4 5 mUA. Levels of 25-80 mUA are equivocal and the infant should be retested. Levels of >80 mUA are abnormal and the infant should be recalled urgently

NEONATAL SCREENING FOR INHERITED DISEASE 197

for full thyroid function tests. Treatment should be started as soon as possible (without waiting for results) with thyroxine 8-10 pgikglday (once-daily dose). The commonest cause of congenital primary hypothyroidism is thyroid dysgenesis (dysplasia). It is associated with trisomy 21, with females affected twice as often as males and with an incidence of 1 in 3500. The second commonest cause is thyroid dyshormonogenesis (autosomal recessive biochemical defectsof iodothyronine synthesis), which has a frequency of 1 in 30000-50 000, equal sex incidence and accounts for 10-15% of infants detected by screening.

Galactosaemia

Galactosaemia has a prevalenceof 1 in 60 000 birthsand screening detects 60-70% while they are still asymptomatic. The effect of screening at 4-6 days upon final outcome is still uncertain. Routine screening is not practised in the UK.

Hereditary tyrosinaemia

Screening for this uncommon disorder is only routine in certain parts of the world, such as Norway, Sweden and Quebec in Canada. There is a defect in fumaryl aceto-acetateand excretion of succinylacetone in urine is diagnostic. Treatment is with low tyrosine and phenylalanine milk. If undetected, there is progressive liver dysfunction, hypoglycaemia, renal tubular defects and eventually cirrhosis. However, a transient tyrosinaemia is commonin preterm infants (respondsto 50 mg vitamin C daily for 1 week).

Cystic fibrosis

DNA analysis now affords a useful screening tool for CF,especially where there is a strong family history of the disorder or one parent is known to be affected. Routinely the commonest mutations are screened for,namelyAF508, 621+1G>T, G542X. G551D and R553X.Absence of these mutations gives an 80% certainty of excluding CF as adiagnosis in the indigenous UK population. An optimal screening programme should screen for the most common mutations in a given population as these vary in different ethnic groups and geographic locations. Meconium ileus in the neonatal period is associated with CF. Fifteen per cent of infants with CF present with bowel obstruction caused by meconium ileus, butonly 75% of infants with meconium ileus have CF. Blood immunoreactive trypsin (IRT) level should be assayed. Elevated IRT (normal values 15OOg, or 233 weeks gestation) to 5 l % (birthweight 6 weeks. Efficacy is also reduced in both the very small preterm infant (c800g birthweight) and infants of high postconceptionalage.Inview of theabove side-effects of indomethacin, ibuprofen, another non-steroidal anti-inilammatory drug,is now also being used, at a dose of10mgkg i.v. followed by 5 mgkg 24 and 48 hours later. Ibuprofen appears as effective as indomethacinbutwithfewer cerebral, gastrointestinal and renal side-effects. Second courses may be given to infants who do not respond to the first course or with recurrentPDA,althoughtheresponse is often poor. Nonresponse to a single coursein infants of l4 mmoVI, creatinine >l40 pmoV1, or persistent oliguria of 2.5 kPa, respectively. Hyperoxia-hyperventilation test. A brief (-10 min) period of hyperventilation induces alkalosis and pulmonary vasodilation with a consequentrise in PaO,. This manoeuvre is associated with increased risk of pneumothorax and further lung damage,particularly as hyperventilation tends to be continued should oxygenation improve. "bo-dimensionalDopplerechocardiography is themost usefulandaccuratediagnostictechnique. Right-to-left shuntingofbloodthroughthePDAandPFOcanbe visualized and the magnitude of pulmonary hypertension estimated from the flow velocity of the regurgitant jet at the pulmonary or tricuspid valve. CHD (especially anomalous venous drainage) can also be excluded at the same time.

I. Stabilize the patient to prevent swings in oxygenntion and other vital parameters 0 Identify and correct any physiological abnormalities likely to increase pulmonary vascular resistance (e.g. hypoglycaemia. acidosis). 0 Sedate (opiates, benzodiazepines) - paralyse to facilitate synchrony with ventilator. 0 Avoidexcessivehandling.

238 PERSISTENT PULMONARY HYPERTENSIONOF THE NEWBORN

Maintain systemic arterialpressure Correcthypotensionwithvolumeexpanders(albumin, FFP, blood) and/or commence inotropes (dopamine, dobutamine). Reduce pulmonary arterial pressure Choice of i.v. and inhaled agents. Assess severit?,of the impairmentof gas exchange. This helps predict the outcome and gauge response to therapy. Use 01for this purpose. Mean airway -pressure (cmH,O) X FiO, X 100% 01 = PaOz (mmHg)

Managementof ventilation

0

0

0

0

0

Intravenous vasodilators

Administersurfactant(whether patient haspneumonia, MAS. or idiopathic PPHN). MAS requires several doses of surfactant. Hyperventilation is nowobsolete as it is associatedwith increased pulmonary morbidity from chronic lung disease and adverse neurodevelopmental outcome (especially sensorineural hearing impairment and impaired psychomotor development). Hypocapnia decreases CBE Inducedmetabolic alkalosis has theoretical advantagesof hyperventilation-induced alkalosis. No studies have evaluatedtheefficacy of this therapy.Hypernatraemiamay ensue from sodium bicarbonate administration. ‘Conservative’ ventilation may be equally effective or superior to hyperventilation. This is deliberate hypoventilation allowinghighPaCO,in order to diminishlung injury. The target pH is 27.25 as compared to 27.5 with hyperventilation. Highfrequency ventilation, particularly HFOV,may be superior to conventional ventilation in improving outcome, as HFOVimproveslungrecruitment.HFJVmay be as effective as HFOV. Vasodilator therapy has a definite role in improving oxygenation in PPHN.

Intravenousvasodilatorsmaybe less effective thaninhaled vasodilators as the former produce concomitant hypotension. The most commonly used i.v. vasodilators are as follows: 0 0 0 0 0 0

Nitroprusside0.2-6 &kg/min. Prostacyclin 1-40 ngkdmin. %D, 1-25 p,gkg/min. Nitroglycerine 0.5-12 pg/kg/min. Tolazoline 1-2 mgkg bolus, followed by 1-2 mgkghour. Magnesiumsulphate 200 mgkg over20-30min followed by 20-150 mgkghour to maintain serum magnesium concentration of 3.5-5.5 mmolA.

PERSISTENT PULMONARY HYPERTENSION OF THE NEWBORN 239

Inhaled vasodilators

Inhaledvasodilatortherapy is dominatedbyNO,therecently discovered potent endogenous vasodilator. Nebulized prostacyclin has alsobeen used, as a selective pulmonary vasodilator with good effect. To date, five randomized trials with over 700 term or near-term infants havebeencompletedinNorth America. ECMO use was decreased in the NO-treated groups (one fewer ECMO patient for every six patients treated with NO). However, up to 40% of infants failed to respond to NO. ECMO is indicated when medical therapyfails andor when the 01>35 (or perhaps lower) with an 84% survival (86% of survivors being neurodevelopmentally normal). ECMOtreated infants do not have increased morbidity compared with infants treated with conventional ventilator therapy.

Prognosis

Deaths from PPHN have decreased in recent years, perhaps due to earlier diagnosis and treatment, with an overall survival rate of 77%.

Further reading Kinsella P, Abman SH. Recent developmentsin the pathophysiology and treatment ofpersistent pulmonary hypertension of the newborn. Journal of Pediatrics, 1995; 126: 853-64. Morin FC, Davis JM. Persistent pulmonary hypertension. In: Spitzer AR (ed). Intensive Care of the Fetus and Neonate. St Louis: CV Mosby, 1996; 506. Truog WE. Inhaled nitric oxide: a tenth anniversary observation.Pediatrics, 1998: 101: 696-7. Walsh-Suskys MC. Persistcnt pulmonary hypertension of the newborn. The black box revisited. Clinics in Perinatology, 1993; 20: 127-43. Yu VYH, Fox WW. Persistent pulmonary hypertension. In: Yu VYH (ed). Pulmonary Pmblems in the Perinatal Period and their Sequelae. Railliere’s Clinical Paediatrics, Vol. 3. No. 1. London: BaillBre Tindali, 1995; 115-30.

Related topics of interest Congenital diaphragmatic hernia (p. 57) Extracorporeal membrane oxygenation (p. 78) Mechanical ventilation (p. 185) Meconium aspiration syndrome (p.189) Nitric oxide therapy (p. 218)

240 PERSISTENT PULMONARY HYPERTENSION OF THE NEWBORN

Marked polycythaemia gives rise to the hyperviscosity syndrome, which is associated with a significant morbidity. Blood viscosityis determined byhaematwrit, red cell deformability and plasma viscosity, the haematocrit being most important. Polycythaemia is present when the central venous haematocrit is 265%. Peripheral venous haematwrits are significantly higher than central ones. The haematocrit rises in the first 24 hours as plasma volume decreases. Prevalence rates of 2-4% have been reported. It is more common in babies bornat high altitude. It is the hyperviscosity secondary to polycythaemia which causes most of the clinical problems. Aetiology

Polycythaemia may be passive (fetus receives transfusion a of red cells) or active (fetus producesexcessivered response to intrauterine stimuli).

cells in

Passive Tivin-twin transfusion. Maternal-fetal transfusion. Delayed clamping of cord. Active

Intrauterine hypoxia (hence elevated levels of erythropoietin), especially placental insufficiencylpre-eclampsia, small-for-gestation infants, post-term infants. and maternal smoking. Chromosomal abnormalities, especially trisomy13, 18 and 21. Severe maternal heart disease. Beckwith’s syndrome. Neonatal thyrotoxicosis. Congenital adrenal hyperplasia. Maternal diabetes.

Pathophysiology

It is unclear whether these symptoms are due primarily to the sluggish circulation and poor oxygen deliveryor the accompanyinghypoglycaemia.Hypoglycaemia is due in part to the high red cell mass and low plasma volume with a low intraerythrocytic glucose level which reduces the overall glucose content of blood. In severe polycythaemia, sludging of the red cells and platelets in asluggishperipheral circulation may occur, resulting in tissue hypoxia and thrombosis.This ismost serious in thebrainwhere it maycauseconvulsionsand infarcts.

Clinical features

Signs commonly appear when the normal physiological reduction in plasma volume occurs (first 24 hours). Hypotoniaandlethargy. Difficulty in arousal.

POLYCYTHAEMIA 241

0 0 0 0 0

Complications

Imtability. Easily startles. Tremulousness. Poor feeding. Vomiting.

1. Early Hyperbilirubinaemia (kernicterus). 0 Cardiac and renal failure. 0 Hypoglycaemia and hypocalcaemia. 0 Respiratory distress. 0 Thrombocytopenia. 0 Seizures. 0 Priapism and testicular infarction. 0 Renal vein thrombosis. 0 NEC. 0 Distal bowel obstruction. 0

2. Late 0 Speech and fine motor abnormalities. 0 Spastic diplegia. 0 Neurodevelopmental delay. 0 Low IQ.

Investigations

0 0

0

e 0 0 0 0 0

Management

242 POLYCYTHAEMIA

FBC. Determine haematocrit by centrifugation (calculated Values from automatic electronic counters are inaccurate and lower than values obtained bycentrifugation). Coagulation screen (in the presenceof thrombocytopenia). Serum bilirubin. Blood glucose. Serum calcium. Abdominal X-ray (suspected NECor obstruction). U&E (in presence of poor renal function). Head ultrasound scan (in presence of seizures).

A partial exchange transfusion replaces infant's whole blood with FFP or 4.5% human albumin (when FFP is not readily available), aiming for a haematocrit of55%. However, crystalloids (e.g. Ringer's solution) may be used effectively. especially if there is hypervolaemiasecondary to twin-twin transfusion. Blood volume to be exchanged is approximately 20mVkg. Alternatively, use the formula: exchange volume = total infant's blood volume (85 m1 X birthweight) X (observed haematocrit minus desired haematocrit) + observed haematocrit. Perform the partial exchange in small volumes (5-10ml aliquots) usingperipheral veins (using umbilicalvessels increases the risk of NEC). For significant symptoms. perform apartial exchange trans-

fusion promptly. For mild or minor symptoms, keep theinfant well hydrated and warm. Screen high-risk infants by performing capillary haematwrit and if this is =65-70% perform venoushaematocrit.Screen for and treat hypoglycaemia.If symptoms do notdevelopwithin 48 hoursandthebaby is feeding well, complications are unlikely.

Further reading Black VD. Neonatal hyperviscosity syndromes. Current Problems in Paediatrics. 1987; 17: 73-130. Delaney-Black V, Camp SW, Lubchenco LO et al. Neonatal hyperviscosity association with lower achievement and IQ scores at school age. Pediatrics. 1989; 83: 662. Hann IM. Gibson BES, LetskyEA (eds). Fetal and Neonatal Haematology.London: Baillihe Tindall, 1991. Oski FA, Naiman L.Hematologic Problems in the Newborn, 3rd edn. Philadelphia: W.B. Saunders, 1982. Ramamurthy RS. Postnatal alteration in haematwrit and viscosity in normal infants and in those with polycythemia. Journal of Pediatrics, 1989; 114: 169-70.

Related topics of interest Anaemia (p. 9) Intrauterine growth restriction (p. 165) Jaundice (p. 173) Transfusion of blood and blood products (p. 323)

POLYCYTHAEMIA 243

POSTNATAL EXAMINATION All infants, including those allowed home within a few hours of birth, should have a full examination within the first day oflife. Ideally the mother should be presentto enable her to askanyquestions she mayhave.Inaddition,anyproblemsnotedcanthen be discussed immediately.

History

As always,theexaminationmustbecomplementedbya history. Quickly note the maternal past obstetric and medical histories (e.g. hepatitis B infection). Notealso significant social problems (e.g. drug abuse, child protection issues) and the family history (e.g. tuberculosis). Finally, run through the pregnancy details and note any complications (e.g. polyhydramnios, abnormal fetal scans), labour (e.g. intrapartumpyrexia)anddeliveryincluding details of the resuscitation, Apgarscoresandbirthweight. Progress since birth (feeding,passageof stools or urineandanyother problems noted) should also be quickly reviewed.

Initial examination

Note age at time of examination. Check weight. length and headcircumferenceandploton centile chart ifnecessary. Undresstheinfantcompletelyandcheckwhetherthe appearanceofthe infant andposture are normal.Note the colour (e.g. pale,cyanosed,jaundiced, plethoric). skin condition (e.g. dry, peeling) and any blemishes. Examine each region in turn starting from the head down.

1. Head and neck. Note shape of skull and check sutures, fontanelle and therest of thescalp (cephalhaematoma?), facies (anyasymmetry,anomalies), eyes (shape, size, epicanthic folds), iris (colobomata), cornea (diameter >l 1 mm and hazy in congenital glaucoma), cataracts (absent red retinal reflex), ears (shape, size, low-set?),nasalairway(checkpatency), mouth (check hard andsoft palate intact), neck (any soft tissue swellings, clavicles intact?). 2. Chest. Shape andbreathingpatternand

effort. Check

heart sounds (murmurs?).

3. Abdomenand genitalia. Noteliver,spleenandkidney size, and number of cord vessels. Feel femoral pulses. Check anus is patent and genitalia are normal with descended testes. If genitalia are ambiguous say so and do not assign a sex!

4. Spine and limbs. Check spine is straight with no dimples and hairy patches. Check upper and lower limbs are of normal shape, havefull range of movements and are symmetrical with normal palmar creases. Check hips have full range of movements and do not dislocate.

244 POSTNATAL EXAMINATION

5. Activity andbehaviour. Notemuscletoneand

activity (symmetricalmovements)withappropriate reflexes (grasp, suck, Moro, step) and normal cry. Asymmetrical movements may suggest birth injury-related palsies (e.g. Erb’s palsy) or a fracture. 6. Special notes. Infantsshouldpassmeconiumwithin 48 hours. Failure to do so suggests bowel obstruction (vomiting, abdominal distension) or anorectal anomalies (e.g. imperforate anus). Passing a small finger per rectum may encourage passage of a meconium plug followed by meconium. Consider the possibility of Hirschsprung’s disease or CF in infants with a meconiumpluganddelayedpassageofmeconium (A8 hours). Serum immunoreactivetrypsin level, stool tryptic activity or a sweattest may be required in the follow-up period. Urine shouldalso be passed within48 hours of birth or look for evidence of urinaryobstructions(enlargedbladder, urethral valves) or reduced urine production (e.g. renal agenesis, renal vein thrombosis, acute tubular necrosis). Ascertain that the infant has received vitamin K prophylaxis. RCG vaccinationshould be givenwhereappropriate (e.g. family historyof tuberculosis) and infants born to hepatitis B-positivemothersshouldreceive hepatitis B vaccine (0.5ml i.m. at birth andrepeated at age 1 and 6 months). Infants whose mothers are e-antigen positive and e-antibody negative should also receive human anti-hepatitis B immunoglobulin (200IU by deep i.m. injection) within 48 hours of birth to confer immediate protection until the vaccine is effective. This should be followed by afull course of vaccinations and a review at 1 year to assess the serological evidence of immunity.

Discharge examination

This is similar to the initial examinationwith some additional points being noted. 0

0

0

Feeding (breast or bottle) should be established. Any parental concerns should be addressed and any questions answered. Marked jaundice should be investigatedanddischarge allowed only if the serum bilirubin is falling or stable. Pendinginvestigationsshouldbediscussed fully and details of follow-up arrangements finalized. Completeandsign (legibly) thedischargerecordwith copies being forwarded to all appropriate personnel in the community.

POSTNATALEXAMINATION 245

Further reading Johnson PB. The Newborn Child, 8th edn. Edinburgh: Churchill Livingstone, 1998. Jones DA. Hip Screening in the Newborn. London: Butterworth-Heinemann, 1998. O’Doherty N.Aflas of the Newborn, 2nd edn. Lancaster: M.T.P. Press, 1985. Roberton NRC. A Manual of Normal Neonatal Care, 2nd edn. London: EdwardArnold, 1996. Thomas R,H a m y D.Neonatology: Colour Guide, 2nd edn. Edinburgh: Churchill Livingstone, 1997.

Related topics of interest Assessment of gestational age (p. 19) Birth injuries (p. 21) Congenital malformations and birth defects (p. 70) Hepatitis R (p. 105) 1mmuni;ration (p. 132) Jaundice (p. 173) Prenatal diagnosis (p. 253)

246 POSTNATALEXAMINATION

PREGNANCY COMPLICATIONS AND FETAL HEALTH As maternal health is intricately linked with that of the fetus, serious complications of pregnancy invariably also affect the fetus. A selection of some of the common complications of pregnancy and their attendant effects on the fetus are presented.

Antepartum haemorrhage This constitutesbleeding from the genital tract from 28 weeks (APW gestation delivery toup fetus. the APH have can of serious consequences for both the mother and fetus. It is associated with a marked increase in perinatal mortality and isalso a significant cause of maternal mortality. The two main causes are placenta praevia and placental abruption. The latter is more serious and is associated with a twofold increase in mortality. 1. Placental abruption. This is due to placental separation with attendant maternal and fetal blood loss (often concealed) and fetal compromise.

(a) Maternal clinical features 0 Painful bleeding from the genital tract. 0 Blood loss out of proportion tomother’scondition, gressing to shock. 0 Uterus tense, tender, irritable and at times hard. 0 Fetal parts and heart rate difficult to ascertain.

pro-

(b) Fetal risks

0

Fetalblood loss and asphyxia. Pretenn delivery (RDS). Intrauterinedeath.

(c) Management Immediate maternal resuscitation with fresh blood transfusion. 0 Coagulation defect..rectified. Fetalviabilityascertainedultrasonically. If fetus is dead, labour induced (after resuscitating mother), aiming for vaginal delivery.

2. Placenta praevia. The placenta encroaches upon the lower uterine segment and may partially or completely cover the cervix.

(a) Maternal clinical features Recurrent painless bleeding from the genital tract. Maternal condition is proportional to blood lost. (b) Fetal risks Pretenn delivery (RDS).

PREGNANCY COMPLICATIONS AND FETAL HEALTH 247

(c) Management Position of placenta ascertained ultrasonically. Emergency delivery by Caesarian section for severe bleeding. Expectant management aiming to prolong pregnancy to 37-38 weeks for minor haemorrhages. Elective Caesarian section at 37-38 weeksfor all but minor degrees of placenta praevia.

Pre-eclampsia

Alsocalled pregnancy-induced hypertension, pre-eclampsia (PE) is characterized by hypertension and proteinuria during pregnancy (mostly third trimester) and immediate puerperium. Severe PE consists of hypertension and proteinuria (M.25gA) and mild PE, hypertension without proteinuria. With an incidence of up to 1 in 10 pregnancies, PE and related hypertensive disorders are still a significant cause of maternal morbidity and death. PE may rapidly progress through the pre-eclampsia state to eclampsia which is characterized by seizures. PE may also develop into a serioushypertensive disorder with elevated liver enzymes, epigastric painandlow platelets (HELLP syndrome).

I . Maternal clinical features Hypertension (blood pressure (BP) 2 140/90) - mild PE. Hypertension with proteinuria - severe PE. Agitation, confusion, visual disturbance, epigastric pain, nausea and vomiting with brisk reflexes - PE state. Seizures (with above) - eclampsia state. 2. Fetal risks Acute or chronic placental insufficiency with IUGR. 0 Placental abruption andfetal asphyxia and intrauterine death. Preterm delivery.

3. Management

0

Preterm rupture of membranes (PROM)

Bcd rest in hospital. Prevention of disease progression to themost severe spectrum. Antihypertensive therapy (methyldopa, hydralazine. pblockers). Anticonvulsant therapy (diazepam, chlormethiazole, magnesium sulphate). For severe disease, prompt delivery by Caesarean section is often necessary.

Before 34 weeks, management of PROM conservative. is Tocolytics (betamimetics) may be used temporarily, affording the opportunity to induce pulmonary maturity by corticosteroids.

248 PREGNANCY COMPLICATIONS AND FETAL HEALTH

I. Fetalrisks Preterm delivery. 0 Pulmonary hypoplasia with prolonged and early PROM. 0 Limb contractures. 0 Idiopathic RDS. 0 Amnionitis andfetalinfection.

0

2. Managemen?. Maternal intrapartum antibiotics following high vaginal and cervical swabs.

Preterm labour and birth

Thisconstitutes labour andbirth before 37 weeksgestation. Prematurity is the single largest contributor to the early neonatal mortality rate.

1. Aetiology and riskfactors Preterm rupture of membranes. 0 Antepartum haemorrhage. 0 Incompetent cervix. 0 PE and related disorders. 0 Poor socioeconomic background. 0 Multiple pregnancy. 0 Polyhydramnios. 0 Maternal infection (e.g. urinary tract infection (UTI)). 0

2. Management Maternal ultrasound scan to assess fetal maturity, growth, presentation and exclude obvious anomalies. 0 Tocolysis if labour not advanced (cervix 30cmH,O), 100% 0, and persisting carbon dioxide retention.

Diagnosis

Management

High-pressure ventilation with persisting CO, retention (as above). Lungfunction tests showareducedfunctionalresidual capacity (FRC) - less than 60% of expected value, i.e. 16mlkg bodyweight.

1. Prenatal. Premature ruptureofmembranesbefore 34 weeks is associatedwith poor outcome.Electivedelivery at 34 weeks may be recommended. Intrathoracic space occupying lesions such as cysts or effusions should be drained in utero to prevent prolonged lung compression. 2. Postnatal. Severepulmonaryhypoplasiamay be incompatible with life. Less severe pulmonary hypoplasia may best be ventilated on high rates and low mean airway pressures. Persistent pulmonaryhypertension of the newborn(PPHN) may be a complicating factor, especially when there is associatedlungdisease(e.g.RDS,sepsis - especiallygroup B streptococcus or meconium aspiration). High frequency oscillation and inhalednitric oxide therapy maybe beneficial. Associatedcongenitalanomalies(e.g.congenitaldiaphragmatic hernia)mayadversely affect theoutcome. ECMO is contraindicated in severe pulmonary hypoplasia. Associated posturalandlimbdeformitiesrespond to physiotherapyand orthopaedic interventions.

Differential diagnosis

The followingconditionsmayco-existandshould ered as alternative diagnoses.

be consid-

Severe RDS. Group B streptococcus pneumonia. Primary PPHN. Neuromuscular disorders (e.g. myotonic dystrophy).

Prognosis

Mortality is high especially in primary pulmonary hypoplasia (over 50%). Associatedanomalies(e.g.renalagenesis or congenital diaphragmatic hernia) increase mortality. Pneumothorax and PIE followed by chronic lung disease and prolonged oxygen-dependency are likely to develop in affected prcterm infants. Long-term lung function may recover completely during the first few years oflife or remain abnormal dependingon the original diagnosis.

262 PULMONARY HYPOPLASIA

Further reading Chemick V, Boat TF (eds). Kendig’s Disordersof the Respiratory Tractin Children, 6th edn. Philadelphia: W.B. Saunders, 1997. Dinwiddie R. The Diagnosis and Management of Paediatric Respiratory Disease, 2nd edn. Edinburgh: Churchill Livingstone, 1997. Halliday HL. Other acutelung disorders. In:Sinclair JC. Bracken MB (eds). Eflective Care of the Newborn Infant. Oxford: Oxford University Press, 1992; 359-84. Keeling JW (ed). Fetal and Neonatal Pathology.London: Springer-Verlag, 1987. Milner AD, Fox G. Congenital abnormalities of the respiratory system. In: Yu VYH (ed). Bailliere’s Clinical Paediatrics, Vol. 3No. 1. Pulmonary Problems in the Perinatal Period and their Sequelae. London: Baillitre Tindall, 1995; 171-202. Spitzer AR (ed). Intensive Care of the Fetus and Neonate.St. Louis: C.V. Mosby, 1996. Swischuk LDE. Primary pulmonary hypoplasia in the neonate. Journal of Pediatrics, 1979; 95: 573-8. Wigglesworth JS. Perinatal Pathology, 2nd edn. London: W.R. Saunders, 1996.

Related topics of interest Complications of mechanical ventilation (p.54) Congenital diaphragmatic hernia (p. 57) Persistent pulmonary hypertension of the newborn (p. 237) Respiratory distress (p. 275) Resuscitation (p. 282)

PULMONARY HYPOPLASIA 263

RENAL AND URINARY TRACT DISORDERS NEPHROLOGY Nephrons develop from the fifth week of intrauterinelife and they are fully formed though not fully functional by 36 weeks gestation. The infant glomerulus is a third of the size of the adult glomerulus, and although the tubules are functioning by 9 weeks, they are short andimmature even at term. Consequently the newborn kidney is functionally immature. The GFR and renal blood flow are low in the newborn period. After birth, GFR increases as a function of postconceptional age ratherthanpostnatalage. A s tubular functionis immature, urineconcentrating ability is limited, as is the ability to excrete a water load. Unlike term infants, preterm infants are unableto conserve sodium. The newborn kidney is therefore vulnerable to several perinatal factors which canadversely affect renal function.

Presentation of renal and urinary tract disorders history Family

0

0

0

Antenatal history

0

History of an inheritedrenal disorder (e.g. polycystic kidney disease - autosomal recessiveand dominant), Alport’s syndrome (X-linked). History of metabolic disorder (autosomal recessive) with renal manifestation (e.g. galactosaemia, cystinosis, tyrosinosis). History of vesico-ureteric reflux (4% risk of reflux in first degree relatives of index patient, but 50% risk if scarring present in index case). Abnormal kidneys on fetal anomaly scan at 17-20 weeks or later (e.g. dilated collecting system, multicystic kidney,

0

0

history Perinatal

0

0 0

0

0

renal agenesis). Oligohydramnios (renalagenesis,dysplasia, urinary tract and Potter’s syndrome). Elevated AFP in amniotic fluid.

obstructed

Placental weight >25% of birthweight congenital nephrotic syndrome, Finnishtype, autosomal recessive, associated with prematurity). Single umbilical artery (urinary tract anomalies in (3%). Delayed micturition (99% of healthy infants urinate by 48 hours) - suggests renal under-perfusion (asphyxia, hypotension, congenital nephritis, urinary tract obstruction, renal agenesis, tubular or cortical necrosis). Oliguria (urinary output lo5 organisms from two clean catch samples or any growth from a suprapubic aspiration sample). Hypertension - mainly renovascular causes, especially renal artery thrombosis.

Specific disorders Acute renal failure

Assume an infant is in renalfailure if urineoutputis < l mVkglhour for 24 hours andor creatinine is >88 pmol/l or urea is >7mmol/l. Thisoccurs in up to 1 in 10 sick newborns.

I . Prerenal failure. This is commonly due to renal underperfusion from: (a) Hypovolaemia 0 Maternal antepartum haemorrhage. FetaVneonatal haemorrhage. 0 Inadequate fluidintake or increased losses(polyuria, insensible loss or gastrointestinal loss). (b) Normovolaemia Asphyxia. Congestive cardiac failure. Septic shock.

2. Intrinsicrenal failure. The main causes are shockand asphyxia. 0

Acute tubular, medullary or cortical necrosis. Arterial or venous thrombosis. Congenital renal anomalies (e.g. agenesis, polycystic kidneys). Congenital infection(e.g. toxoplasmosis or syphilis) and DIC. Uncorrected prerenal failure.

3. Post-renal failure. 0 Ureterocele.

RENAL AND URINARY TRACT DISORDERS- NEPHROLOGY 265

e 0

Clinical features of renal failure

0

e e 0 0 0

Investigations

Pelvi-ureteric or vesico-ureteric junction obstruction. Urethral obstruction - (posterior urethral valves, urethral stricture, urethral diverticulum, tumours, neurogenic bladder). Hyperkalaemia (major cause of death from cardiac toxicity). Hyponatraemia (dilutional). Hypertension (from volume overload). Metabolic acidosis (inability to excrete acids). Hyperphosphataemia and hypocalcaemia. Sepsis (a major cause of death).

1. Blood e

e e 0 0

e 0

e

U&E and creatinine. Glucose. Calcium and magnesium. Albumin. Acid-base status. FBC and film. Blood culture (full septic screen if sepsis suspected). Coagulation studies.

2. Urine e Microscopy (casts). e Dipstick. e Culture. e Urea and creatinine. 0 Electrolytes. e Osmolarity.

3. Others e e 0

Management

Renal ultrasound scan. Weigh infant. Check blood pressure.

Establish the diagnosis of renal failure and differentiate between thethreemain causes of renal failure, astheir management differs. Confirm obstructive uropathy on ultrasound examination and refer to aurologist. Distinguishing pre-renal from intrinsic renal failure may be difficult, but the followingindices may be helpful. In pre-renal failure, urindplasma osmolarity is >2 (c1 intrinsicfailure),urine sodium l0 (10ml/kg over 3 hours), there is renal under-perfusion and continue with careful rehydration. If fluid volume is replete but hypotensive, try an inotrope (e.g. dopamine 5-2Opgkglmin). If fluid challenge fails, severely cut back fluids, only replacing insensible water loss plus measured fluid andelectrolyte losses (weighinfant).Correctsevereacidosis(pH 6 mmoM +.ECG changes) with resonium enemas, 10% calcium gluconate (slow i.v.) or bicarbonate (i.v.). Monitor serum electrolytes regularly plus ECG. Administer calcium supplements and phosphate-binding agents as required. If plasma sodium 8 mmol/l, bicarbonate < l 2 mmol/l with creatinine %30pmoyl with severe fluid overload not responding to the above measures, consider peritoneal dialysis. Treat suspected infection (after all cultureshave been obtained)with nonnephrotoxicdrugs.Hypertension(commonly due to fluid overload)responds to fluid restriction. As renalfunction improves, ease fluid and dietaryrestrictions and finally remove them as renal function returns to normal.

Renal artery thrombosis

Thisis associatedwithahighumbilical artery, sepsisand hypercoaguable states. Physical signs includehypertension, haematuria, proteinuria, oliguria, congestive heart failure and, if bilateral, minimal or absent renal function. Renal ultrasound scan is normal but radionucleotide (['3'IJHippuran) uptake is absent. Treat hypertension aggressively as prospects for full recovery are good.

Renal venous thrombosis Thisis associatedwithdehydration,asphyxia, hyperosmolality, cyanotic CHD and incidence is increased in IDMs. Common signs include flank or abdominal mass, haematuria andthrombocytopenia.Ultrasonographyshowsanenlarged kidney with thrombus in the renal vein or extending into the inferior vena cava. Management is supportive with correction of predisposingfactorsandrenal failure (if it develops). Prognosis is generally good. Nephrotic syndrome

Nephrotic syndromeis rare in the newborn. Causesof neonatal nephrotic syndrome include congenital nephrotic syndrome of Finnish type, epimembranous nephropathy due to renal vein thrombosis.congenital syphilis or hepatitis B anddiffuse mesangial sclerosis. InFinlandprevalence is 1.2 per 10000 births. The placenta is large (25% of birthweight, normal 18%) andclinicalsignsincludeoedema, heavy proteinuria, hypoalbuminaemia and elevatedcholesterol. The proteinuria is unresponsive to immunosuppressive drugs and corticosteroids. Renalhistologyshowsdiffuseproximaltubule dilatation.

-

RENAL AND URINARY TRACT DISORDERS NEPHROLOGY 267

There is severefailure to thrive and frequentbacterial infections. Management is symptomatic - salt restriction, diuretics, antibiotics for sepsis and optimizing calorie intake. Penicillin therapy is curative for the nephrotic syndromedue to congenital syphilis. If diagnosis is uncertain, renal biopsy is essential for an accurate diagnosis, prognosis, guiding therapy and parental counselling.

Renal tubular acidosis

(RTN

This is a group of disorders caused by an impaired to acidify urine. Three types are recognized.

ability

I . Distal RTA (type I ) . This is due to impaired distal acidification (an inability to lower urine pH below5.5 in the faceof systemic acidosis). Presenting clinical features include polyuria,hypercalciuria,potassiumdepletionand failure to thrive. 2. Proximal RTA (type 2). This is due to impaired HC0,reabsorption in theproximaltubulewithadecreasedrenal HC0,- threshold. 3. Hyperkalaemic RTA (type 4). There is impaired acidification due to impaired renal ammoniagenesis. There is a normal ability to acidifyurine after anacidloadbutnetacid excretion is subnormal due to decreased excretion. It is seen in infants with hypo- or pseudohypoaldosteronism. Suspect RTA when metabolic acidosis is accompanied by hyperchloraemia and normal a plasma anion gap, i.e. [Na'+ K'] - [Cl- + HCO,-] = 8-16 mmoVI. A normal anion gap reflects HC0,- loss from the kidneys or gastrointestinal tract. Distinguishproximalfrom distal RTA fromtheurine aniongap:aurinesamplefromapatientwithhyperchloraemicmetabolicacidosisandanegativeurineanion gap suggests proximal RTA, while a positive anion gap suggests distal RTA. Oral alkali (sodium citrate or sodium bicarbonate) is the therapy of choice for RTA with oral diuretics (thiazide or frusemide) to reduce serum potassium in type 4 RTA.

N H ;

Hypertension

Hypertension is defined by systolic blood pressure >90/60 in termand >80/45 in preterm infants. Commencetherapyif systolic pressure is persistently >100mmHg and diastolic >75 mmHg. Over 75% of neonatal hypertension is secondary to renal artery thrombosis while approximatelyone in five may be due torenal artery stenosis. The correct cuff shouldbe used (width 2% of upper arm length)withthe infant at rest. Symptoms and signs include those of underlying disorder and hypertension itself (hypertensiveencephalopathy, seizures, congestive cardiac failure). Treatment depends on the cause.

-

268 RENAL AND URINARY TRACT DISORDERS NEPHROLOGY

Hypertension secondary to volume overload responds to fluid restriction, diuretics (e.g. frusemide 0.5-2 mgkgldose 12hourly or chlorothiazide 5-10 mglkg/dose 12-hourly), vasodilators (e.g. hydralazine 1-5 mgkglday given 6-hourly, captopril 0.1-1 .Omgkg/day given &hourly) or 13-blockers (e.g. propranolol 2-5 mglkgldaygiven 8-hourly). Monitor electrolytes when diureticsare used. For urgent control of hypertension, i.v. nitroprusside (0.5-5 pgkglmin) or diazoxide (3-5 m a g ) are useful. Investigate persistent hypertension to exclude renovascular disease, coarctation of the aorta, other intrinsic renal or post-renal disease and adrenal disorders.

Further reading Awutu M, Hunley TE, Kon V. Pathophysiology of acute renal failure in the neonatal period. In: Polin RA, Fox WW (eds). Fetal and Neonatal Phvsiology,2nd edn. Philadelphia: W.B.

Saunders, 1998; 1691-6. Rroin LP, Satlin LM. Clinical significance of developmental renal physiology. In: Polin RA, Fox WW (eds). Fetal and Neonatal Physiology, 2nd edn. Philadelphia: W.B. Saunders, 1998; 1677-91. Postlethwaite RJ (ed). ClinicalPaediatricNephrology. 2nd edn. Oxford: ButterworthHeinemann, 1994. Proesmans W (ed). Therapeutic Strategies in Children with Renal Disease. Railli2reS Clinical Paediatrics, Vol. 5, No. 4. London: Bailli2re Tindall, 1997.

Related topics of interest Acid-base balance (p. 3) Blood pressure (p. 34) Fluid and electrolyte therapy (p. 87) Renal and urinary tract disorders - urology (p. 270)

RENAL AND URINARY TRACT DISORDERS- NEPHROLOGY 269

RENAL AND URINARY TRACT DISORDERSUROLOGY Polycystickidney disease This canoccur as anautosomaldominant (adult polycystic (PCKD) disease, ADPCKD) form or autosomal anrecessive form (infantile polycysticdisease,ARPCKD).InARPCKD.the main site of dilatation is the collecting tubules. The severe form is rapidly fatal at or soon after birth. An i.v. pyelogram is characteristic (mottled nephrogram and retention of contrast with delayed excretion). The kidneys are massive, and those infants surviving the first month experience increasing renal failure and hypertension. Liver biopsy shows hepatic fibrosis with biliary dysgenesis. ADPCKD presents similarly with renal failure and reduced renalfunctionwithprogressiverenalinsufficiency.Nephrosonography shows bilateral large and small renal cysts. Imaging studies cannotaccuratelydistinguishARPCKDfrom ADPCKD. In ADPCKD, there is usually a family history of PCKD and parents often show hepatic or renal cysts when imaged (Cr or ultrasound scans). ADPCKD has a better prognosis than ARPCKD. Renal cystic dysplasia

When unilateral, thetermmulticystickidney is used. There are large cysts with little renal tissue. It is commonly detected prenatally. Always examine the contralateral kidney carefully as anomalies (e.g. pelvi-ureteric junction (PUJ)obstruction) are common. The non-functionalkidneymayrequire surgical removal (risk of neoplasia). Renal cystic dysplasia is associatedwith other anomalies,such as theZellwegercerebrohepatorenal syndrome and Meckel-Gruber syndrome. A 99m-technetium-labelleddimercaptosuccinicacid ([w”’Tc]DMSA) scan is required to determine whether the kidney is functional.

Renal agenesis

The completeabsenceofbothkidneys is rare (1 in loo00 births). There is oligohydramnios and associated pulmonary hypoplasia with Potter’s facies, bowed legs, clubbed feet. no kidneysevidentonprenatal scans andaffected infants die perinatally or are stillborn.

Posterior urethral valves

This only occurs in males. The bladder is distended and the urine stream is poor. Diagnosis is confirmed by renal ultrasoundandmicturatingcystourethrogram(MCUG)though most still present acutely unwell with a UTI. The immediate managementconsists of drainingtheurinary tract viaan indwelling catheter, commencing broad-spectrum antibiotics

270 RENAL AND URINARY TRACTDISORDERS - UROLOGY

and i.v. fluid andelectrolyte therapy. A paediatric urologistwill be required to resect the valves. Some infants, however, eventually develop renal failure and require renal transplantation.

Hydronephrosis

This is readily diagnosed antenatally (renal pelvis >8-10mm diameter after 34 weeks) and should be confirmed postnatally (48-72 hours). If hydronephrosis is confirmed, antibiotic prophylaxis should be commenced (trimethoprim 2mg/kg once daily) until MCUGhasbeenperformed to ruleoutvesicoureteric reflux. To determinewhethera dilated kidney is obstructed, [99”Tc]-mercapto-acetyl-triglycerine-3 (MAG-3) with a diuretic may be helpful. If obstruction is suspected seek a paediatric urological opinion. Otherwise regular follow-up with repeatrenal ultrasound scans isrequired with a high index of suspicion for intercurrent UTIs. In time the hydronephrosis resolves along with the needfor antibiotic prophylaxis.

Hypospadias

In hypospadias, the urethral meatus may be positioned just below the glans way back at the root of the penis. In severe cases, the penis is short and curved (due to chordee) resembling alarge clitoris, causing problems in assigning a sexto the infant. If both testes are present in the scrotum the infant is male, but when absent the infant could be a female with the adrenogenital syndrome, or incomplete testicular feminization may be suspected. It is vital then that the infant’s karyotype, endocrine status andpelvicanatomy be ascertained (ultrasound or laparotomy) as it may be preferable to rear some ‘genetic males’as ‘females’ if their internal genital tract is easier to convertsurgically to afemaleconfiguration.Infants should not be circumcised prior to surgical repair.

Vesico-uretericreflux

Vesico-uretericreflux(VUR) is theconsequenceofanincompetent vesico-ureteric valve mechanism and may resolve spontaneously or, infrequently, lead to chronic renal insufficiency. There is an important genetic componentto non-obstructive or ‘idiopathic’VUR. One-third of the siblings of affected children will also have VUR, while 60% of the offspring of parents with VUR will also be affected. VUR also occursinapparently healthy infants and children (asymptomatic VUR), the incidence falling from birth to age 4 years, and is more commonin boys ( 4 l). VUR associated with UTI (symptomatic VUR) is, however, predominantly found in girls, with a 4:1 preponderance. VUR is more common in infants presenting with UTI (30-5095) and in infants with prenatal hydronephrosis. VUR can cause morphological (renal scars) andfunctionalrenal damage. Renal damage is more likely with gross VURand bladder dysfunction (e.g. neurogenic bladder). Renal scars are caused by intrarenal reflux, bacterial infection (UTI) andor

-

RENAL AND URINARY TRACT DISORDERS UROLOGY 271

obstruction acting in concert. The rapidly growing kidney (i.e. infants andtoddlers) is mostsusceptible to morphological damage. VUR predisposes to arterial hypertension.

I. Diagnosis of VUR. MCUG, is the ‘gold standard’. It visualizes the urethra, bladder and renal pelvis. permitting grading of severityof reflux. Indirect radionuclide voiding cystography (e.g. MAG-3 renogram) is less reliable and can onlybe used in the older continent child. MCUGs should be performed in all infants presenting with prenatal dilatation of the renal pelvis, family history of VUR, UTI and acute pyelonephritis. 2. Management of VUR. The goal of medical therapy is to avoid UTTs by using antibiotic prophylaxis and regulation of bladder and bowel emptying. The optimum duration of prophylaxis is not known but is influenced by severity of VUR, intercurrent UTIs and associated anatomical abnormalities (see below).Surgery is indicatedinpatientswith dilating VUR (grade 2111) whoseparentsprefer an operation or arenoncompliantwithmedicaltreatment.However,medicaland surgical treatments are almost equally effective in protecting kidneys from new damage or the progression of pre-existing damage.In4.2% of patients, surgery is complicatedby obstruction. Follow-up untilVUR resolves or the risk of complications is minimal. Spontaneous resolution of VUR may be ascertained in the older continent child by indirect (i.v.) isotope cystography which avoids catheterization and minimizes exposure to radiation.

Urinary tract infection

This is confirmedbythefindingofapuregrowthofasingle pathogen at a count of at least IOs colony-forming units/ml urine in at least two clean specimens of urine, or any growth from a suprapubic aspirated urine specimen. Pus cells may be present or absent. Absence of growth from an appropriately handled bag specimen can rule out UTI. The commonest predisposing factor is urinary stasis (VUR. bladder dysfunction, infrequent or incompletevoiding,outflowobstruction as in urethral valves). In the first 2-3 months of life, UTI occurs predominantlyinboys,between3-12months of age boys and girls areequally affected, andabove 1 year girls are predominantly affected.

l . Clinical features. In infants symptoms are non-specific, including:

0

Fever. Jaundice. Failure to thrive. Feeding difficulties.

272 RENAL AND URINARY TRACT DISORDERS - UROLOGY

Vomitinganddiarrhoea. Occasionally as severe illness with cyanosis, hypotension and shock.

2. Immediate investigations Bloodandurine cultures. FBC. U&Eand creatinine. Lumbar puncture (if particularly unwell). Renalultrasoundscan. Urinemicroscopyofafreshuncentrifugedclean sample identifies infection (eight organisms per high power field, or IO’ organisms/ml) and allows treatment to be started while awaiting cultureresults. Dipslides canalso give reliable results within 24 hours.

3. Management. Aim to establish a prompt diagnosis, rapid treatment and detection of any underlying cause that might predispose to further infection or lead to long-term renal damage. If thereis a strong suspicion of UTI. a start treatment once a clean sample has been obtained. Antibiotics covering common causative organisms (Escherichia coli, Enterococcus spp.. Klebsiella spp., Streptococcusfaecalis, Proteus ssp., Pseudomonas spp.). Commence initial combination (e.g. ampicillin and gentamicin) until sensitivities are available, then switch to the most appropriateantibiotic(s) for 5-7 days (uncomplicated UTI) or 10 days (systemically unwell). If the infantis systemically unwell, usei.v. antibiotics until the infant is improved and has been apyrexial for 24-36 hours before reverting to oral antibiotics. Add a third-generation cephalosporin (e.g. cefotaxime) if meningitis is suspected. Maintain on prophylactic antibiotics (e.g.trimethoprim 2 mgkg once daily) until VUR is excluded. Monitor fluid and electrolytes in infants presenting with dehydration or systemic illness. Monitor BP. Check post-treatment urine without stopping prophylaxis. Persistence of infection. mixed infection or early recurrence with a resistant strain suggests bladder dysfunction or outflow obstruction. Follow-up investigations (several weeks later) MCUG (to detect VUR). DMSA scan after 23 months (to identify renal scamng). Urinalysis and urine microscopyat follow-up.

RENAL AND URINARY TRACT DISORDERS - UROLOGY 273

Check BP at follow-up (hypertension and proteinuria are markers of progressive renal disease). Continuelong-termprophylaxis if reflux or scamng is present until child is 2-3 years. Advise parents to have infant reassessed if fever or symptoms recur despite prophylaxis. Reinfectionwithanorganism sensitive to prophylactic therapy suggests non-compliance, infection with resistant organismrequiresfull-dosetreatmentandadjustment of prophylaxis. In absence of renal anomalies, follow-upis required for at least 1 year and ideally until the child has been infectionfree for 2 years.

Imaging in renal disorders

Ultrasound scan is a mandatory first-line investigation in any renal disorder. Intravenous urography (IVU) is the investigation of choicein elucidating suspected anatomical abnormality. [w"'Tc]-DMSAis the investigationof choice in elucidatingsuspected renal parenchymal damage(scars). MCUG is the investigation of choice in determining the presence and severity of VUR. MAG-3 renogram is the investigation of choice when determining the quantitative excretory function of individual kidneys and possible outflow obstruction (when a diuretic is also administered).

Further reading Obling H. Vesico-ureteral reflux (VUR).In:Proesmans W (ed). TherapeuticStrategies in ChildrenwithRenalDisease.Bailli&re'sClinicalPaediatrics, Vol. 5, No. 4. London: Raillitre Tindall, 1997; 521-38. SmellieJM.Managementandinvestigation of childrenwithurinary tract infection. In: Postlethwaite RJ (ed). ClinicalPaediatricNephrology, 2ndedn.Oxford:ButterworthHeinemann, 1994. Thomas DFM (ed). Urological Disease in the Fetus and bqant: Diagnosis and Management. Oxford: Butterworth-Heinemann. 1997.

Related topics of interest Fluid and electrolyte therapy (p. 87) Infection - neonatal (p. 143) Renal and urinary tract disorders - nephrology (p. 264)

274 RENAL AND URINARY TRACT DISORDERS- UROLOGY

Respiratory problems, manifestas respiratory distress, are the commonest cause of admission of newborns to the neonatal unit in the perinatal period. Respiratory distress arises from inadequate in urem maturation of the lung and of mechanisms controlling respiration, or from disease processespresentbefore or after birth whichcompromisepulmonaryfunction. The causes and management of respiratorydistress vary depending on the gestational and chronological age of thc infant. Aetiology

1. Preterrn infants (a) Respiratory 0 Surfactantdeficiency. Pneumothorax. 0 Chroniclungdisease. 0 Pulmonaryhaemorrhage. 0 Pulmonaryinsufficiencyofprematurity. 0 Congenitallungmalformations(e.g. cystic adenomatoid malformation). (b) Infection Pneumonia. Septicaemia. Meningitis. (c) Miscellaneous Cold stress. 0 Hypoglycaemia.

2. Term infants (a) Respiratory 0 Pneumothorax. 0 Pleural effusion. 0 Transient tachypnoea of the newborn. 0 Meconiumand other aspirationsyndromes. 0 Congenitalmalformations(e.g. cystic adenomatoidmalformations, pulmonary lymphangiectasia, pulmonary hypoplasia,CDH,congenitalnasolacrimal duct obstruction (congenital dacryocystocele)). 0 PPHN. Congenitalsurfactantprotein B deficiency. (b) Cardiovascular Congenital heart defects leading to heart failure (hypolastic left heart syndrome, obstructed total anomalous pulmonary venous drainage, severecoarctation). (c) Infection 0 Pneumonia. 0 Septicaemia. Meningitis. (d) Miscellaneous 0 Cold stress.

RESPIRATORY DISTRESS 275

0

0

Polycythaemia. Maternal drugs (e.g. opiates). Birthtrauma and birth asphyxia. Neuromuscular disorders (e.g. spinal muscular atrophy type 1. myotonic dystrophy). Inherited metabolic disease (e.g. organic acidaemias).

Clinical features

The characteristic features are tachypnoea, grunting, nasal flaring and cyanosis, whichmay be superseded by apnoeas or acute collapse. In addition, cardiac murmurs, abnormal peripheral pulses or signs of cardiac failure may also be present if there is an underlying congenital heart defect.

Investigations

1. Pulse oximetry. It is useful to determine the arterial oxygen saturations as a guide to the severity of hypoxaemia and the urgency ofintervention.

2. Temperature. Exclude hypothermia or pyrexia.

3. Blood glucose. Exclude hypoglycaemia. 4. Arterial blood gases. This is essential to determine the degree of respiratory failure and decisions on the next most appropriate interventions to be made. Capillary or venous blood gases may be misleading in an infant with poor peripheral perfusion. Inordinate persistent metabolic acidosis may point to a metabolic disorder.

5. Chest radiograph. Rule out pneumothorax, effusions, pulmonary oedema, abnormal cardiac silhouette, congenital diaphragmatic hernia; bell-shaped chest is seen in neuromuscular disorders, and ground glass appearance with idiopathic RDS, congenital pneumonia or aspiration. 6. FBC and film. Sepsis suggested by low or high white blood cell count and thrombocytopenia.

7. Full septic screen. This should be conducted when there is a high suspicion of sepsis. 8. ECG and echocardiogram. These are conducted for suspected cm.

Management

This isdetermined by the underlying diagnosis. Aim to correct acid-base disturbance and alleviate hypoxaemia and respiratory failure. Warm cold infants and correct hypoglycaemia. Preterm infants with RDS and significant hypoxaemia should be intubated for surfactant administration and mechanical ventilation. However, infants with mild RDS may be immediately extubated after surfactant administration and maintained on CPAP. More mature infants (>34 weeks gestation) withmild RDS may be managed on CPAP or

276 RESPIRATORY DISTRESS

headbox oxygen with recourseto mechanical ventilation when the FiOz exceeds0.6, if blood gasesare unsatisfactory, or there are apnoeas. Transient tachypnoea of the newborn usually resolves with minimalsupport(supplementaloxygen).Unlessthesupplemental oxygen requirementsare modest, anarterial line should be sited for blood gas monitoring in oxygen-dependent infants. Suspected sepsis should be promptly treated with an appropriate combination of broad-spectrum antibiotics until cultures are available. Pneumothoracesandsymptomaticeffusions should be drained appropriately and repeat radiographs performed to determine the adequacy ofthe procedure. Infantswithsuspected CHD or malformationsrequiring corrective surgery are best managed in specialist centres and may require ventilation for safe transportation. PGE, or PG& should be commenced in infants with suspected ductdependent congenital heart lesions and a paediatric cardiology opinion sought.

Further reading Fanaroff AA, Martin N. Neonatal-Perinatal Medicine: Diseases of the Fetus and Neonate, 6th edn. St Louis: Mosby, 1997. Gluckman PD. Heyman MA (eds). Pediatrics and Perinatology: The Scient@c Basis,2nd edn. London: Arnold, 1996. Hamvas A. Cole S, deMello DE et al. Surfactant protein B deficiency: antenatal diagnosis and prospectivetreatmentwithsurfactantreplacement. Journal of Pediatrics, 1994; 125: 356-61. Philip AGS. Neonatology: A Practical Guide, 4th edn. Philadelphia: W.B. Saunders, 1996. Taeusch HW, Ballard RA (eds). Avery’s Diseasesof the Newborn,7th edn. Philadelphia:W.B. Saunders, 1998.

Related topics of interest Acid-base balance (p. 3) Congenital diaphragmatic hernia (p. 57) Congenital heart disease - congestive heart failure (p. 61) Infection - general (p. 139) Intubation (p. 170) Maternal drug abuse (p. 182) Mechanical ventilation (p. 185) Meconium aspiration syndrome (p. 189) Respiratory distress syndrome (p. 278)

RESPIRATORY DISTRESS 277

RESPIRATORY DISTRESS SYNDROME RDS, previously called hyaline membrane disease, is the single most important medical disorder in preterm infants, affecting 40-50% of all infants born before 32 weeks gestation. It is primarily a consequence of respiratory failure secondary to cardiopulmonary immaturity in preterrn infants. Avery and Mead first demonstrated in1959 that the lungs ofinfants with RDS were uncompliant due to surfactant deficiency. Attempts to prevent RDS have therefore concentrated on ways of enhancing the action or accelerating production ofsurfactant. Accelerating lung morphological maturity is also essential. The incidence and severity of RDS is inversely proportional to gestational age (or birthweight). Ininfants R 7 weeks gestation, RDS is almost universal andafter 27 weeks but before 32 weeks, RDS may affect two in three infants. After 32 weeks RDS is less frequent and tends to be moderate regardlessof other risk factors. Mortality during the acute phaseis now largely confined to ELBW infants (l week therapy weangradually. Long-term follow-up studies up to the age of 5-6 years do not show adverse neurodevelopmental effects in preterm

SEDATION AND ANALGESIA ON THE NlCU 291

infants who received morphine for sedation during mechanical ventilation.

2. Diamorphine. Diamorphine is morelipid soluble than morphine, andhas a more rapid onset of sedation and less hypotensive effects. Its side-effects profile is similar to morphine. The loading dose is 120 p g k g (over 2 hours) followed by a continuous infusion of 15 pgkghour. 3. Fentanyl. This is a synthetic opioid 80-100 times more potent that morphine. It has a more rapid onset of action (peak effect in 1-2 min when given i.v.), and a short half-life with very few haemodynamic effects (decreased histamine effects). Following a loading dose of 1-4 pgkg, a continuous infusion of 1-2 pgkghour provides effective analgesia. Side-effects include a higher rate of withdrawal symptoms, a more rapid development of tolerance and chest wall rigidity with rapid large-dose infusions. 4. Paracetamol. This is well suited for minor discomfort or pain(e.g. after immunizations) andmay be repeated 4-6hourly at a dose of 10 mg/kg/dose.

5. Kefamine. Ketamine is a fast-acting phencyclidine derivative which is both a sedative and potent analgesic. Its effects are apparent within 1-2 min and last 5-10 min. The standard dose is 0.5-1 mg/kg followed by a continuous infusion at 5-20 pgkg/min. Ketamine increases heartrate, cardiac output, BP and CBE

6. Midatolam. This short-acting, water-soluble benzodiazepine is a commonly used sedative especially in ventilated infants. It is metabolized in theliverand excreted in the urine. It has a rapid onset (1-5 min) butthehalf-life in neonates is 6-12 hours. Clearance is reduced andhalf-life increased in neonates compared to older infants. The loading dose is 100-200 p g k g and the continuous infusionrateis 1-2.5 pgkg/min. Concurrent administration of fentanyl with midazolam may produce dystonic movements and hypotension.

7. Chloral hydrare. Chloral hydrate is a hypnotic and sedative agent well tolerated by neonates at 30-50 mg/kg. The parent drug and its active metabolite trichloroethanol have long half-livesandtherefore a potential for accumulation with repeated dosage. It has no respiratory depressant or analgesic effects. Sideeffects include cardiac arrhythmias, gastrointestinal irritability and paradoxical agitation. Trichloroethanol may compete withbilirubin for hepatic glucuronidation. 292 SEDATION AND ANALGESIA ON THE NICU

Toxic effects from prolonged use include hypotension, renal failure, CNS depression and carcinogenicity. 8. Massage. The stress responsemay also bereducedby non-pharmacological means, e.g. stroking or massage.

Muscle relaxation

Routine muscle relaxation is not advocated. However, some critically ill ventilated infants may benefit from paralysis, e.g. mature infant.. with ventilator asynchrony or CDH. Complications ofparalysisincludedeterioration of gas exchange, obscuring seizures, pain or agitation, tissue oedema, muscle contractures and myopathy. Muscle relaxants should be given concurrently with analgesics, as infants would still feel pain.

1. Suxamethonium. This has the most rapid onset of action (1 min) and shortest duration of action (4-6 min), making it ideal for emergencies. It may be used to facilitate intubations. The dose is2 mgikg i.v. or 4 mgikg i.m. The onset of actionis slower (2-3 min) and duration of action longer (10-30 min) when given im. 2. Pancuronium. Pancuronium is metabolized in the liver and excreted in urine (delayed excretion in renal failure). It raises BP, cardiac output and heartrate. The dose is100 p g k g i.v. (effective in 3 min and lasting 60 min). 3. Vecuronium. Vecuronium has fewcardiovascular sideeffects and is metabolized and excreted by the liver (in bile), although in neonates renal excretion is important. The dose is IO0 pgikg i.v. (effective in 2 min andlasting 30 min) followed by infusion of 1-3 pgikglmin.

Further reading Alexander SM, Todres ID. The use of sedation and muscle relaxation in the ventilated infant. Clinics in Perinatology, 1998; 25: 63-78. Bucher H-U. Bucher-Schmid A. Treating pain in the neonate. In: Hansen TN, McIntosh N (eds). Current Topics in Neonatology, No. 1. London: W.B. Saunders, 1996; 85-1 10. Lawrence J, Alcock D, McGrath P, Kay J, MacMurray SB, Dulborg C. The development of a tool to assess neonatal pain. Neonatal Network, 1993; 12: 59-65. Sparshott M. Pain, Distress and the Newborn. Oxford: Blackwell Science, 1996.

Related topics of interest Anaesthesia and post-operative analgesia (p. 13) Birth injuries (p. 21) Intubation (p. 170) Mechanical ventilation (p. 185) Neonatal surgery (p. 200) Respiratory distress syndrome (p. 278)

SEDATION AND ANALGESIA ON THE NlCU 293

A seizure is sudden a paroxysmal depolarization of a group of neurones resulting ina transient alteration in neurological state. This may involve abnormal sensory, motor or autonomic activity, with or without a change in conscious level. Seizures generally are indicative of another underlying disease process and very few are idiopathic (2-5%). Seizures are a fairly common occurrence in the neonatal period with an incidence of 1-3 per IO00 live births at term. The incidence may be up to 50 times greater in preterm infants. The incidence of electrographic but clinically silent seizures is unknown, but upto 80% of electrographic seizures may be clinically silent especially in preterm infants. The primary objective of any intervention is to control the seizures, determine causation and rapidly correct any treatable causes as this may improve prognosis.

Seizure types

There are four types of clinical seizures: subtle, tonic, clonic and myoclonic. Each can be focal, multifocal or generalized.

I. Subtle seizures. The most common variety (-50% of all seizures), manifested by apnoea, eye fluttering and deviation, staring, sucking and chewing, cycling, boxing, unstable blood pressure and tachycardia, 2. Clonic seizures. Making up -20-30% of all seizures, these are more common in preterm infants and are typified by rhythmic jerky movements (1-4/s) with consciousness usually preserved. They may be focal, suggesting a focal underlying lesion, such as cerebral artery infarction (but may also result from metabolic derangements), or multifocal. 3. Myoclonic seizures. Contributing -15% of all seizures, these are rapid isolatedjerks especially of the upper limbs, signifying metabolic or major structural derangement. They may be focal, multifocal or generalized. 4. Tonic seizures. Making up -5% of all seizures, these are typified by sustained focal or generalized posturing ofthe body. such as tonic extension of all limbs, pronation of arms and clenching of fists. Generalized tonic seizures often signify more serious pathology, for example severe IVH.

It is important to distinguish jitteriness and apnoeas from seizures. Jitteriness is characterized by a symmetrical tremor of the extremities (spares the face) occurring at a higher frequency (5-6/s) than clonic movements. Jitteriness can be induced byan external stimulus and ceases with gentle restraint. Apnoeas may be a manifestation of subtle seizures, especially in term infants and when the apnoea is not accompanied by bradycardia andis associated withstaring, eye opening or deviation of eyes.

294 SEIZURES

Aetiology

I. Hypoxic-ischaemic encephalopathy (HIE).Thisis the commonest cause, accountingfor half of the cases of neonatal seizures. Moderate HIE tends to present with subtle and clonic seizures, while severe HIE may present with myoclonic and tonic seizures. The seizures present in thefirst 24 hours. may 2. CNS infection. Prenatal or perinatal infection account for up to one in five cases of neonatal seizures. The commonest bacterial pathogens are group B streptococcus, E. coli and Listeria sp. Herpes simplex encephalitis and other pre.natal infections should also be excluded. 3. Intracranial haemorrhagehnfarction. Following birth trauma in terms infants, subarachnoid and subdural haemorrhages may cause seizures independently from any co-existing asphyxia. IVHs with or without periventricular haemonhagic infarction can cause generalizedtonic seizures. The above causes may account for 10-15% of neonatal seizures. 4. Metabolic derangements. These may account for 1 in 10

neonatal seizures, the commonest being hypoglycaemia, hypocalcaemia, hypomagnesaemia and hyperor hyponatraemia. IMD (e.g. urea cycle defects, aminoacidurias and organic acidopathies) though rare should be considered when there is a positive family history, persistent acidosis, unusual odours or seizuresunresponsive to conventionaltherapy. Rarely, IMD maypresentwithsevererecurrentseizures (myoclonic and clonic) and a burst-suppression EEG pattern, and early myoclonic encephalopathy. Pyridoxine dependency is a rare autosomal recessive defect in gamma-aminobutyric acid (GABA) synthesis which presents with early onset refractory seizures which are abolished by administering pyridoxine (50-100 mg).

5. Maternaldrug addiction. Neonatal drug withdrawal is an important cause of neurological dysfunction though only 1 in 20 will develop seizures. Methadone withdrawal seizures may occur as lateas 3 weeks though most otherdrugs produce symptoms earlier (3 seizureshour) or prolonged seizures (>3 min duration) especially if they adversely affect systemic blood pressure or respiration. As many anticonvulsants cause respiratory depression and impair myocardial function, blood pressure and respiratory activity should be monitored.

Drug therapy

1. Phenobarbitone. This i s a very effective first-time monotherapy controlling up to 70% of all seizures. Loading dose is 20mglkg i.v. (may be repeated, giving a total of 40 mglkg) and maintenance is 6 mg/kg/day (given 12-hourly). Half-life is 3-8 days andthe serum therapeuticlevelis 90-180 mmoVI. Phenobarbitone is a free-radical scavenger and reduces calcium entry afterischaemia.

296 SEIZURES

2. Clonazepam. This second-line drug is most useful when seizure control is poor. The loading dose is 100-20Opglkg (i.v. over 30s) followed by an infusion of 10-30pg/kghour. Convert to oral once-daily dose when seizure control is achieved. Other benzodiazepines such as lorazepam may also be useful. Diazepam has a very short duration of action and marked respiratory depressive effect making it unsuitable for long-term therapy. 3. Phenytoin. This is useful for securing short-term seizure controlandnot for long-term use as it causes myocardial depression and has very variable metabolism. Loading dose is 20 mglkg (i.v. at 90% of cases in the UK) 210H2la-hydroxylase 11 0 H 1 1Phydroxylase (5% of cases in the UK)

l

I

Figure 1. Simplified steroid biosynthetic pathways

’l”1. Summary of the effects of specific enzyme defects

eteinVirilization Defect

20,22D 3P-HSD 170H 210H 110H

girls

masculinization of boys

No

Yes

No

Yes Yes No No

Yes Yes

300 SEXUAL AMBIGUITY

Salt loss

Hypertension

Yes Yes No 50%Yes No

No

No No Yes

2. Malepseudohermaphroditism. There is incomplete virilkation of a genetic male with testes. This may be due to: (a) Impaired metabolism of androgens by peripheral tissues Sa-reductase deficiency is an autosomal recessive defect, in which the internal male organs (testosterone-dependent) develop normally, but the external genitalia (DHTdependent) are ambiguous, and the phallus is small. Testicularfeminization: androgen receptor/post-receptor defects in whichthe end organs do not respond to the androgens present as a spectrum of abnormalities, from an apparently normal female (but sometimes withbilateral inguinal hernias with a testis in them) to an infertile male. (b) Impaired testosterone production (rare)

0

3. Abnormal gonadal differentiation True hermaphroditism occurs when an individual has both testicular tissue with seminiferous tubulesandovarian tissue with follicles. They may combine as an ovotestis or be separate gonads. Some present at birth with abnormal genitalia, others only at pubertywhen secondary sexual characteristics do not develop normally. Eighty per cent are XX, 10% XU, 10% mosaic. Asymmetrical gonadal dysgenesis - a testis on one side and streak gonad on the other. XX males frequently havetheSRY gene translocatedto the paternal X chromosome.

Further reading Hughes IA. Management ofcongenital adrenal hyperplasia. Archives ofDisease in Childhood. 1988; 63: 1399-1404. Levine LS, Pang S. Prenatal diagnosis and treatment of congenital adrenal hyperplasia. Journal of Pediatric Endocrinology, 1994; 7: 193. McGillivray BC. Genetic aspects of ambiguous genitalia. Pediatric Clinicsof North America, 1992; 39:307-17. Warner GL, Hughes IA. The clinical management of ambiguous genetalia. In: Brook CGD (ed). Clinical faeditric Endocrinology, 3rd edn. Oxford: Blackwell Science, 1995.

Related topics of interest Acute collapse (p. 6 ) Congenital malformations and birth defects (p. 70) Postnatal examination (p. 244) Prenatal diagnosis (p. 253)

SEXUAL AMBIGUITY 301

Shock constitutes a medical emergency where prompt and appropriate action can to lead a full recovery, whereas delayed though appropriate action may be inadequate to save the patient’s life. A state of shock implies a generalixd inadequacy of blood flow and tissue perfusion throughout the body, resulting in tissue damage. It can develop insiduouslyor rapidly progress to an irreversible stage. Shock may be categorized according to its aetiology into septic, hypovolaemic, cardiogenic, anaphylactic and neurogenic. Despite the varied aetiology, the clinical features are remarkably similar.

Clinical features

m m

m m m m m m m m

Management

Generalized pallor. Ill looking. Cold peripheries. Poor capillary refill. Weak or impalpable pulses. Tachycardia and hypotension. Cyanosis and mottled skin. Tachypnoea and/or laboured breathing. Metabolic or mixed acidosis. CNS depression and hypotonia.

Resuscitative measures must be instituted before any detailed examination. Improve oxygen delivery to tissues Administer oxygen by face maskor bagging. Intubate and ventilate if there is severe respiratorydistress, respiratory failure or marked acidosis. Improve cardiac performance Restore circulating blood volume if hypovolaemic (administer 15-20 mlkg of 4.5% albumin, F P , blood or normal saline, then reassess). If nothypovolaemic,givea 10mYkg volumechallenge (colloid or normal saline) to increase venous return. Improve myocardial contractility by: (a) Correcting acidosis Commence artificial ventilation and/or administerNaHCO, (or THAM) ifpH c7.25, and reassess. (b) Administering inotropes Dopamine infusion (5-20 p,g/kg/min)preferablyvia central line as there is risk of tissue necrosis. Adrenalineinfusion (0.1-1 p,g/kg/min) if insevere shock.

3. Determine the likely cause by reviewing riskfactors Suspect infection inthepresenceofpreceedingtemperature instability, fever or hypothermia,long lines, feed

302 SHOCK

e

e

e

e

e

Investigations

e

e e

e e

intolerance and respiratory instability (e.g. apnoeas). Promptly institute antibiotics (empirically) following appropriate cultures (blood, urine and CSF). Suspect cardiac cause in the presence of gallop rhythm, pulse differential (brachiallfemoral),cardiomegaly, murmur(s),hepatosplenomegaly,lungcrackles or cyanosis. Beware of cardiac tamponade especially with indwelling central lines and muffled heart sounds. Perform echocardiography and removecentral line immediately if tamponade isconfirmed. Aspirate pericardial effusion. Suspecta pulmonarycause in thepresence of reduced breath sounds (tension pneumothorax), vomitus or blood in oropharynx (aspiration of vomitus or pulmonary haemorrhage), tachypnoea and grunting. Suspect anaphylactic reaction if drugs and/or blood products have recentlybeen administered or are currently being administered. Discontinue any ongoing parenteral medications or blood products and give adrenaline (1:lOOOO at 0.1 mVkgi.v. - minimum 1 ml). May repeat this after 5 min. Hydrocortisone (5-10mg/kg i.v.) may be given in a severe reaction. Observe patient over the next24 hours. Suspect intra-abdominal cause in the presence of abdominaldistensionand/or bilious vomiting(NEC +perforation) - place a nasogastric tube and emptythe stomach to decrease risk of aspiration. Suspect adrenal insuficiency ifhyponatraemic,hyperkalaemic, 2 hypoglycaemic and dehydrated. Arterial blood for acid-basebalanceandbloodgases, FRC, coagulation studies, U&E, creatinine and glucose. Chest X-ray and abdominal X-ray (with abdominal signs). Infection screen (urine, blood, 2 CSF culture). LP may be delayed. Remove suspect vascular lines and send tips for culture. Swab any surgical wounds or infected sites. Echocardiography (with cardiac signs). Cranial ultrasound scan (intracranial haemorrhage).

Further reading Donn SM, Faix RG (eds). Neonatal Emeqencies. Mount Kisco, NY: Futura Publishing CO, 1991.

Related topics of interest Acid-base balance (p. 3) Acute collapse (p. 6 )

SHOCK 303

The skin structure of a full-term neonate is the same as that of an adult, apart from thedermis which is thinner. All four layersof the epidermis arepresent by 24 weeks gestation but the epidermis is much thinner in pretenn infants c34 weeks, in particular the stratum corneum (outer layer). Bamer function is poor with the potential for high water losses and increased absorption of topical applications. Physiological skin lesions: Milia. Vernix caseosa. Harlequin colour change. Cutis marmorata. Physiological scaling. Sucking blisters. Sebaceous gland hyperplasia. Lanugo hairs in preterm.

Vesiculopustular lesions

The majority of neonatal skin lesions are vesiculopustular and lesions fall into four categories - transient rashes, infections and infestations, genodermatoses and naevoid disorders. The history of appearance and distribution of lesions is helpful in differentiating between these causes.

1. Transient rashes Miliaria. Due to blockage ofthe eccrine sweat ducts.If blockage issuperficialthenclear, thin-walled vesicles (miliaria crystallina) are seen, whereas itchy red papules (miliaria rubra) are present if the blockage is lower down in the epidermis. They are typically seen in thefirst 2 weeks of life. Erythematoxicumneonatorum. Present in upto 50% of neonates and typically presents in the first48 hours of life. Skin lesions range from erythema to urticarial papules and pustules which contain eosinophils. It may recur beyond the first month of life. 0 Transient neonatal pustulosis. Commoner in neonates with blackskins.Superficial fragile pustules containing neutrophils are present at birth and rupture easily (sometimes in utero) to leave a pigmented macule with a collarette of scale. Macules may last for 3 months. 0 Infantile acropustulosis. Presents inthefirst 3 months of life. Recurrent crops ofitchy I-4mm vesiculopustules containing neutrophils and sometimes eosinophils aretypically seen on the hands and feet.Lesions cease by the second or third year. 0 Eosinophilicpustular folliculitis. A rare condition with male predominance. Lcsions may be present at birth and

304 SKIN DISORDERS

come in recurrent crops of white/yellow pruritic papules which tend to affect the scalp, hands and feet. Neonatalacne. Relativelycommon, particularly closed comedones on the nose, forehead and cheeks. Open comedones, inflammatory papules and pustules may occur. It tends to resolve within 1-3 months without scarring. Infections and infestations Bacterial - impetigo,staphylococcalscaldedskinsyndrome. Herpes virus infections - HSV, VZV, CMV. Fungal - candida, pityrosporum. Parasitic - scabies. Genodermatoses Epidermolysishullosa(autosomaldominantandrecessive). A group of inherited disorders with an abnormal tendency to blister formation. The severity depends on the level of cleavage in the skin. Incontinentia pigmenti (X-linked dominant).Usually presentsin thefirstfew days of life withvesiculobullous lesions. These last for a few weeks and are followed by warty papules. It is usually lethal in utero in males. Naevoid disorders (a) Urticaria pigmentosa (mastocytosis) e Reddish-brown macules which urticate when rubbed may be present shortly after birth. Lesions usually resolve by Puberty. (b) Naevi Salmon patchesare flat pink lesions presentat birth usually on the upper eyelids, glabella or nape of the neck. They graduallyfadealthough IO-20% ofthose on theneck may persist. Port wine stain (naevus flammeus). This deep reapurple lesion is present at birth and does not change with time. Strawberrymarks are usuallynotpresent at birth but develop in the first few weeks, initially as a flat lesion and subsequently becoming raised and red. Sebaceous naevus. This is an oval or linear yellow-orange warty lesion typically affecting the scalp. There isa risk of neoplastic change after puberty. Giant pigmented naevus (bathing trunk naevus). This extensive brown pigmented naevusis present at birth and carries a risk of malignant melanoma. Treat by dermabrasion in the first week of life. (c) Congenital ichthyoses e Collodianbaby. The baby is red andcoveredinashiny translucent membrane.

SKIN DISORDERS 305

Harlequin fetus. Thickplaqueswith body surface.

fissures coverthe

It is important to start treatment without delay. Nurse in a high-humidity incubator and apply a greasy emollient such as white soft paraffin and liquid paraffin in a 5050 mixture to the skinevery 2 hours.Fluidrequirementsmay be as high as 200-250 mVkg and need close monitoring. (d) Neonatal lupus erythematosus This presents within the first few weeks of life as an erythematous scaly rash, typically around the eyes, and may be associated with heart block. There may be no history of SLE in themotherbutthere is placentalpassageof antibodies most commonly anti-Ro (anti-SSA). (e) Developmental abnormalities 0 Aplasia cutis. There is localized absence of skin most commonly affecting the posterior scalp. An ulcer is present at birth and heals slowly withscamng. 0 Amnioticbanddeformities.

0

Further reading Harper J. Handbook of Paediatric Dermatology. 2nd edn. London: Buttenvorth-Heinemann. 1990. Rook A, Wilkinson DS, Ebling FJG, Champion RH, Burton JL (eds). Textbookof Dermatology, 5th edn. Oxford: Blackwell Scientific, 1992. Van h a g MC, Van Rooij RW, Folkers E, Spritzer R, Menke HE, Oranje AP. Diagnosis and treatment of pustular disorders in the neonate. Paediatric Dermatology, 1997; 14: 131-43.

Related topicsof interest Congenital malformations and birth defects (p. 70) Postnatal examination (p. 244)

306 SKIN DISORDERS

STRIDOR Stridor is the noise produced on inspiration or expiration due to abnormal narrowing of the upper airway (tracheaor larynx). Inspiratory stridor is more common. The aetiology is varied, includingbothcongenitalandacquiredcauses.Persistent stridor intheneonatalperiod requires investigation.

Aetiology

I . Subglottic srenosis. This may result from the trauma of endotrachealintubationespecially if prolonged, or maybe congenital. Inspiratory and expiratory stridor is present. 2. Laryngomalacia. This is due to floppy aryepiglottic folds and inspiratory stridor predominates and is worsened by lying in a supine position but relieved by lying prone.The cry is normal. This isthe least serious of causes and generally improves with growth.

3. Vocal cord palsv. This is associated with respiratory distress, inspiratory stridor and difficulties in feeding. 4. Tracheal compressions. This may be external(e.g.vascular strictures from double aorta or anomalous vessels) or internal (e.g. subglottic haemangiomas and papillomas) producing inspiratory and expiratory stridor. Subglottic haemangiomas commonly coexist with cutaneous haemangiomas.

5. Miscellaneous. Laryngeal clefts, websandother rarer congenital malformations mayalso produce stridor, respiratory distress andfeeding difficulties. Some rare disorders, for example Pelizaeus-Merzbacher disease may also be associated with stridor.

Clinical features

Very mild stridor maynot be associatedwithobvious physical signs. Moderate to severe stridor is accompaniedby tracheal, sternal and intercostal recession. Severe stridor is not influenced by posture. Tachycardia may be a sign of impendingcollapse. The obligatoryexcessrespiratoryworkinmoderate to severe stridor may cause failure to thrive. Cutaneous capillary haemangiomasmay be associated with subglottic haemangiomas.

Investigation

Pulse oximetry. Anterior-posterior chest X-ray and lateral view of neck. Barium swallow (vascularrings). Fibreoptic laryngoscopy. Microlaryngoscopy. CT scan (vascular rings).

STRIDOR 307

Management

Laryngomalacia generally improves over time, but where there isserioushypoxaemia,surgery may berequired (e.g. supraglottictrimming) but it may be difficultto avoid tracheostomy. Systemic steroids may be used with benefit to treat significant subglottic haemangiomas and postextubation stridor. Congenital laryngeal and tracheal anomalies may require specialist surgical correction. Vascular rings may requireresection or re-arrangement.Rarely, tracheostomy may be required.

Further reading Chernick V, Boat T.Kendig’s Disordersof the Respiratory Tractin Children,6th edn. Philadelphia: W.B. Saunders, 1997. Dinwiddie R. The Diagnosis and Management of Paediatric Respiratory Disease, 2nd edn. Edinburgh: Churchill Livingstone, 1997. Freeland AP. The laryngologist in the neonatal unit.In:Gray RF, Rutha J (eds). Recent Advances in Otolaryngology. Edinburgh: Churchill Livingstone. 1988; 109-24. Quiney RE, Gould SJ. Subglottic stenosis: a clinicopathological study. Clinical OtolatygolOQ, 1985; 10: 315-27. Richardson ME.Otolaryngology {PediatricVolume),3rd edn. St. Louis: C.V. Mosby, 1998.

Related topics of interest Complications of mechanical ventilation (p. 54) Congenital malformations and birth defects (p. 70) Intubation (p. 170) Respiratory distress (p. 275)

308 STRIDOR

In 1980, Fujiwara and co-workers were the first to show a benefit from intra-tracheal surfactant instillation in preterm babies with RDS. They used a modified bovine surfactant; other natural surfactants have been derived from bovine or porcine lungs and human amniotic fluid. Synthetic surfactants are composed mainly of dipalmitoyl phosphatidylcholine (DPPC. or 'lecithin') that lowers surface tension, and a spreading agent such as tyloxapol and hexadecanol or unsaturated phosphatidyl glycerol. Presently they do not contain surfactant proteins. Early trials of both natural and synthetic surfactants showed a reduction of about 40% in mortality from RDS and a similar reduction in pneumothoraces compared to control babies whodidnotreceive surfactant. The incidence of IVHs is notgreatly affected, butPDA, pulmonary haemorrhages and apnoeas are slightly more frequent in surfactant-treated babies. PDA and pulmonary haemorrhages bothresult from an early lowering of pulmonary vascular resistance, which increases pulmonary flow andleft-to-right shunting through the duct andso fills up the pulmonary vasculature. Pulmonary haemorrhage - best thought of as pulmonary haemorrhagic oedema - is seen in about 4% of surfactant-treated babies. Delayed ventilator pressure weaning may help reduce the incidence. Apnoeas occur more frequently as babies come off the ventilator sooner. After these earlystudies, further questions were asked about the use of surfactantsin babies with respiratory distress. It is now clear that: 0

0

Early treatment with surfactant is better than late. Natural surfactants are more effective than synthetic ones. Surfactant therapy benefits babies with meconium aspiration. It may also be beneficial in congenital pneumonia, CDH, PPHN, pulmonary haemorrhage, as a transient therapy in infants with congenital deficiency of the surfactant-associated protein SP-B. and in the 'adult' (or 'acute') respiratory distress syndrome (ARDS) where natural surfactants (which contain SP-B and SP-C) may be superior to synthetic surfactants (which do not contain proteins). The timing of surfactant treatmenthas been divided into:

1 . Prophylactic surfactant given at birth or before respiratory distress develops. 2. FArly treatment given as soon as moderate respiratory distress develops in a baby and preset thresholds are passed - e.g. a mean airway pressure of 7 mbar or FiOz 3. Late treatment (rescue therapy) given only when severe RDS is present.

Late treatment is the least effective of these approaches, and is no longer used. The debate now is whether babies at risk should receive surfactant at birth or just as early as possible during respiratory distress, perhaps even being intubated solely for surfactant administration, then extubated and puton nasal prong CPAP iftheir disease is mild. There is little doubt that preterm babies who receive surfactant within minutes of birth benefit more than those who receive it early in the disease, evenif this is only 1-2 hours later. The cost of givingit at birth to all babies of(say) c32 weeks is prohibitive because only20-40% of the more mature babies in this group would go on to need ventilation and surfactant. They are the most numerous, and also those least likely to die and/or develop chronic lung disease. The clinical benefits and the benefitkost ratio increase inversely with gestational age. so many units give surfactant atbirth only to babies between 23-24 weeks and 27-28 weeks gestation. Others give it to all babies

SURFACTANT REPLACEMENTTHERAPY 309

c32 weeks gestation as soon as they are intubated, whether that is at birth, or some time later if they develop respiratorydistress. Head-to-head trials have compared natural with synthetic surfactants. Compared to those treated with the synthetic surfactant, babies treated with a naturalone had odds ratios (OR) of 0.8 for neonatal mortality, 0.86 for the combined end-point of chronic lung disease and death, and 0.53 for pulmonary air leaks (not every commercially available surfactanthas been evaluated in such trials). Natural surfactants also act more quickly.This isbecause of the presence of the surfactant-associated proteins SP-B and SP-Cthat help in the adsorption and spread of the surfactant. SP-A and SP-D are removed during the extraction process. Both play arole in host defence mechanisms, and SP-A is involved in the local recycling of surfactant. To date. head-to-head clinical trials comparing two natural surfactants with each other (e.g. SurvantaTM versus Infasurf", or Survantam versus CurosuflM)have not shown major differences in long-term outcome (e.g. mortality and chronic lung disease) between these preparations. The phospholipid content of a normal surfactant pool has been estimated to be approximately 100mg/kg bodyweight. Preterm infants with RDS may have only 5 mg phospholipid per kg. Most surfactant manufacturers recommend doses of lOOmg phospholipid per kg bodyweight suspended in3-5 m1 of saline per kg. Manufacturers' dosing and redosing recommendations have ranged from arelatively restrictive use to a more liberal use (e.g. multiple doses given every 6 hours if the baby remains intubated and requiring >30% oxygen). On average, two to threedosesaregiven,but in conditionscharacterizedbysurfactant inactivation, multiple doses may be more effective. Respiratory diseasein term infants causes abnormalities in surfactant metabolism. Meconium displaces and inhibits surfactant, and the increased capillary permeability in pneumonia leadsto surfactant inactivation by fibrin. Treatment is aimed at reversing or overwhelming this pathology. Optimal dosing schedules for this have yet to be established, but 6-hourly aliquots of 150-200% of the normal dose, starting soon after birth, have been used in some trials.

Further reading Barrington W, Finer NN. Care of near-term infants with respiratory failure. British Medical Journal, 1997;315: 1215-58. Findlay R D , Taeusch H W , Walther FJ. Surfactant replacement therapy for meconium aspiration syndrome. Pediatrics, 1996;97: 48-52. Fujiwara T, Maeta H,Chida S et al. Artificial surfactant therapy in hyaline membrane disease. Lancet, 1980;i: 55-9. Halliday HL. Natural versus synthetic surfactants in respiratory distress syndrome. Drugs, 1996; 51: 226-37. Kattwinkel J. Surfactant: evolving issues. Clinics in Perinatology, 1998;25: 17-32. Kattwinkel J, Bloom BT, Delmore P et al. Prophylacticadministrationofcalfsurfactant extract is more effective than early treatment of respiratory distress syndrome in neonates of 29 through 32 weeks' gestation. Pediatrics, 1993;92: 90-8. Long W (ed). Surfactant replacement therapy. Clinics in Perinatology, 1993;20(4). Morley CJ. Systematic reviewof prophylactic versus rescuesurfactant. Archives of Disease in Childhood,Fetal and Neonatal Edition, 1997;77: WO-4. Robertson B. New targets for surfactant therapy: experimental and clinical aspects. Archives of Disease in Childhood,Fetal and Neonatal Fdition, 1996;75: FI-3.

310 SURFACTANT REPLACEMENT THERAPY

Related topicsof interest Mechanical ventilation (p. 185) Meconium aspiration syndrome (p. 189) Persistent pulmonary hypertension of the newborn (p. 237) Pulmonary haemorrhage (p. 259) Respiratory distress syndrome (p. 278)

SURFACTANT REPLACEMENT THERAPY 311

SURGICAL EMERGENCIES In a minority of deliveries. the newborn infant may require acute life-saving intervention for cardio-respiratory support or immediate andrapid assessment for a variety of congenital anatomical defects that require urgent attention. The greatest assets in dealing with any infant with a problem in the immediate newborn period are anticipation and a team approach. Anticipation of a problem is commonly based on antenatal diagnosis by ultrasonography. When there is ample warning before the delivery, the asembled team can best decide on the timing, route and site of delivery. Infantswith complex congenital defects will require transfcrto atertiary paediatric surgical centre. Maternal transfer to an appropriate maternity unit facilitates the infant's postnatal care. Despite all the advances in antenatal diagnosis. some newborn infants may still be found to have unexpected anomalies requiring urgent surgical attention. In addition, previously well neonates may also develop acute medical disorders requiring urgent surgical attention.

Conditions presentingat birth Abdominal wall defects

0 0

Gastroschisis. Ectopia vesicae.

Management Cover the defect(s) with dry sterile dressing andor plastic covering (e.g. cling film). 0 Obtain venous access and administer colloid to support the circulation - if necessary. Administer an infusion of 10%dextrose to maintain normal blood glucose. Obtain bloodfrominfantand mother for blood grouping and cross-matching. Refer to a paediatric surgical service.

Anomalies of the gastrointestinaltract

0

Oesophageal atresia. TOE Small bowel obstruction (e.g. duodenal or ileal atresia) with or without perforation.

Management Withholdoralfeeds. 0 Obtain venous access and maintain normal blood glucose by administering an infusion of 10%dextrose. 0 Nasogastric suctioning to decompress the stomach and constant oropharyngeal suctioning toclear pharyngeal secretions (oesophageal atresia). 0 Obtain maternal and infant's blood for grouping and crossmatching. 0 Refer to a paediatric surgical service.

312 SURGICAL EMERGENCIES

Urological anomalies

0

0 0

Posterior urethral valves. Severe bilateral hydronephrosis. Ureteric rupture and urinary ascites. Bilateralpelvi-ureteric junctiodvesico-uretericjunction obstruction.

Management 0 Confirm prenatal findings with postnatal ultrasound scan. 0 Catheterize infants suspected of havingposteriorurethral valves. 0 Obtain urgent MCUG and refer to paediatric urologist. 0 For suspected bilateral pelvi-ureteric/vesico-ureteric junction obstruction anduretericrupture,refer immediately to apaediatric urologist. Commence prophylactic i.v. antibiotics.

Cardiacanomalies

As most of these anomalies are not diagnosed untilreferralto a specialist paediatric cardiology centre, early referral to such a centre. is therefore desirable. A handful of lesions require earlysurgicalintervention if chances of survivalareto be enhanced. The main conditions are: 0

0

0

0

HLHS. Coarctation of the aortalintempted aortic arch. Obstructed total anomalous pulmonary venous drainage. TGA with intact ventricular septum. Pulmonary atresia with intact ventricular septum. Complex congenital heartlesions. Tricuspid atresia.

It is essential to commence a PGE, infusion (0.05-0.1 pg/kg/min) in infants suspected of having ductdependent lesions at the earliest opportunity. Correct metabolic acidosis and commence treatment for heart failure (if present) with diuretics (e.g. frusemide 1-2 mg/kg/dose). Intubation and mechanical ventilation may be necessary. Once the infant is stabilized,transfer to a paediatric cardiac centre.

Specific disorders

1. Congenital diaphragmatic hernia. If previously diagnosedantenatally,avoid bagging to preventaerationand expansion of intrathoracicbowel.Intubate immediately at birth. Proceed to surgery when the infant has stabilized (see ‘Congenital diaphragmatic hernia’).

2. Torsion of the testes. Thisisa

realemergency as the affected testis must be operated on within a few hours or it becomes non-viable. The affected testis is higher, often larger and, if recently twisted, very tender. This may occur prenatally. in which case the enlarged bluish testis is non-tender. Urgent exploration is required to untwist the testis, if still viable, or

SURGICAL EMERGENCIES 313

orchidectomy, if non-viable, with orchidopexy being performed on the contralateral side.

Conditions presenting later These are mainly gastrointestinal in nature and are summarized below: 0 0 0 0

Intra-abdominal perforationwithperitonitis. Strangulated hernias (inguinal, femoral). NEC. Volvulus.

Occasionally a variety of other acute medical conditions may arise and require an urgent surgical input.These include acutethromboembolic phenomena, accidents with vascular lines (e.g. snapped central intravascular lines with a retained distal portion), major subdural haemorrhages, serious post-operative wound dehiscence, and serious accidental injuries.

Management

0

0

0

0

0

0

Commence nasogastric drainage to decompress the abdomen. Withhold oral feeds and commence infusion of a dextrose electrolyte tomaintain normal blood glucose. Administer analgesia as a continuous i.v. infusion whenever infants are, or are likely to be, in pain. If surgery is likely to result in significant blood losses, obtain infant’s blood for grouping and cross-matching. Administer colloid to support the circulation (where necessary). Unless an expert opinion is already availableon site, transfer to an appropriate paediatric surgical service.

Further reading Black JA,Whitfield ME Neonatal Emergencies: Early Detection and Management,2nd edn. Oxford: Buttenvorth-Heinemann, 199 1. King LR. Urnlogic Surgeryin Infants and Children.Philadelphia: W.B. Saunders, 1998. O’Neill Jr JA.Rowe MI, Grosfeld JL, Fonkelsrud EW, Coran A.Pediatric Sueery, 5th edn. St Louis: Mosby, 1998.

Related topics of interest Congenital diaphragmatic hernia (p. 57) Herniae (p. 108)

314 SURGICAL EMERGENCIES

Necrotizing enterocolitis (p. 195) Neonatal surgery (p. 200)

Thermoregulation is the ability to maintain a normal body temperature in varying environmental conditions and temperatures. When these protective homeostatic mechanisms are overcome. body temperature rises or falls outside the normal range. The thermal stresses a baby may have to deal with include: 0 0

Excessive cooling from evaporation, radiation, convection and conduction. Excessive heating from high environmental temperatures and humidity, radiant heaters and over-wrapping.

Cooling

Thereis a clearly establishedrelationshipbetweenhypothermiaandincreasedmortalityandmorbidity,andprompt attention to temperature controlis mandatory. Hypoxia reduces the ability of thebaby to respond to acold stress, so the asphyxiated baby andor the baby with respiratory distress are at particular risk. Evaporation of amniotic fluid from the skin of a newborn babyis a common cause of cooling immediately after birth, even in tropical environments or warm rooms. Such evaporation can drop a term baby’s temperature as much as 2°C in 15 min. Rapid drying and wrapping reducethis fall. but many commercially available radiant heaters will not. Heat is radiated from a naked baby who is a ‘hot spot’ radiating heat to its cooler surroundings. Significant radiant heat loss occurs from the head, so dressing a baby includes putting a hat on. Convective and conductive heat losses in a dressed baby are minimal, providing bedding and clothes are at body temperature when put on, and the baby is not in a draught, which would also increase evaporative cooling. Preterm and small-for-dates babiesare particularly prone to hypothermia because of their: 0

0

High surface area to body size ratio. Lack of subcutaneous adipose tissue that helps insulate the body. Poor energy stores and limited brown fat deposits. Babies respond to cooling with: Reduction of heat loss by peripheral vasoconstriction and the assumption of the fetal position to reduce the exposed surface area. Extraheatproduction. This involvesthereleaseofnoradrenaline that acts locally in the brownfat deposits to stimulate lipolysis and hence heat production. For this to be successful there must be adequate oxygenation of the tissues and a good circulation. Glucose will also be metabolized for heatproductionandhypoglycaemiamust

THERMOREGULATION 315

therefore be avoided.Newborn themselves through shivering.

infants cannotwarm

Thennoneutrality

A baby with

Over-heating

Largerbabiescanbecomeoverheatedunderphototherapy lamps, radiant heaters, insideclosedincubators or if overwrapped in a warm room. As best their circumstances allow, they will respond to this by:

a normal temperature who is trying neither to increase heat production, norto increase heat loss, is said tobe in a thermoneutral environment. Incubators should therefore be capable of providing a thermoneutral environment for a range of babies at different ages. The environment must be defined not just in terms of temperature but also humidity, convection (draughts) and surrounding radiant heat sources. A well,week-old, 3.5 kg babyneedslowerenvironmental temperatures than a small, extremely preterm one on the first day, when temperaturesin excess of 37°C and high humidity in a draught-free environment may be necessary if the baby is naked.

0

Increasedheat loss throughperipheralvasodilatationand increasing the exposed surface area by adopting a ‘sunbathing’ posture. Sweating. However, term babies are able to achieve only a modest increase in cooling through sweating - much less than children or adults - and preterm babies have even more limited sweating. If the child is over-swaddled, then the responseto heat stress can be very limited and the baby becomes hyperthermic. Panting. This limited response to heat stress which persists for some weeks after birth, together with the inability to wriggle free of bedclothes and clothing, contributes to the risk of cot-death in over-swaddled babies.

Further reading B a c k K. Neonatal thermal regulation. In: Polin R, Fox WW (eds). Fetal and Neonatal Phvsiology, 2nd edn. Philadelphia: W.B. Saunders, 1998; 676-702. Okken A, Koch J (eds). Thermoregulation of Sick and Low-birthweight Neonates. Berlin: Springer, 1995. Sinclair JC. Management of the thermal environment. In: Sinclair JC, Bracken MB (eds). Effective Care of the Newborn Infant. Oxford: Oxford University Press, 1992; 40-58.

Related topics of interest Neonatal surgery (p. 200) Resuscitation (p. 282)

316 THERMOREGULATION

Transport of sick neonates (p.327)

TRACE MINERALS AND VITAMINS Eight trace minerals are nutritionally essential for humans: chromium, copper, iodine, iron, manganese, molybdenum, selenium and zinc. They play vital roles in several metabolic pathways. Clinical deficiencies have been described for six of the minerals. As accretion of trace minerals occurs during the last trimester of pregnancy, prematurity is associated with low stores at birth and the premature infant is at incrcased risk of developing trace mineral deficiencies.

Chromium

Chromium is involved in glucose homeostasis and this is the only biological role postulated for this micromineral. Chromium deficiency hasnot been described in infants. Human milk has 0.3-0.5pg chromiud andthe chromium content of preterm human milk is unknown. The recommended enteral chromium intakeis 0.1-0.5pgkgIday. and 0.050.2 pglkglday (0.2 pglkglday in the . preterminfant) parenterally. There are no data to justify intakes higher than that received by the breast-fed infant. Copper is contained in several enzymes including cytochrome oxidase and is required for connective tissue formation, myelinization and iron utili7ation. The most abundant coppercontaining enzymes are the superoxide dismutase enzymes, which protectcellmembranesagainstoxidativeinjury. Caeruloplasmin, representing 60% of the copper in plasma and theinterstitialfluids,isa weak oxidase and primarily transports copper from its storage sites in theliverand muscles. Deficiency state (copper W% (may be prevented in infants receiving large transfusions by irradiating the blood prior to transfusion which inactivates the T lymphocytes responsible for TA-GVHD).

Transfusion reactions

There are two importantserologicaldifferencesbetween infants and older children or adults. First, infants have IgG antibodiesderivedfrom thematernal circulation which gradually decline during the first few months of life. Second, infants have a poor response to antigenic challenges such as allogenicred cell antigens. Thus whentransfusedwithred cells that differ from their own, infants do notrespondby making alloantibodies until after the third month of life. Any antibodies detected in a newborn’s blood sample are maternal in origin. Therefore, if an infant’s initial antibody screen is negative, blood of an appropriate blood groupcan be issued to theinfantwithout the need for furthertyping or crossmatching for thefirst 3 months of life. Transfusionreactions are therefore relatively rareinthe newbornperiod,butwhenthey occur theymay be lifethreatening. A transfusion reaction maybe immediate or occur after several days or weeks. Immediate reactions include fever (often due to antileucocyte antibodies), allergic reactions (anaphylaxis or urticaria), acute haemolysis and a haemonhagic state. Delayed reactions include the development of haemolysis and sensiti7~tion tored cell antigens, making later crossmatching more difficult and predisposing the infant to more transfusion reactions. An acutehaemolyticreaction due to incompatible bloodis serious as it can result in acute renalfailure and DIC. Symptoms include fever. bleeding and shock. The transfusion must be discontinued, blood bank notified and the blood pack returned to the blood bank along with 3-5 ml of the infant’s blood (clotted sample), and BP and urine output should be monitored. Treat shock, if present, appropriately (see

324 TRANSFUSION OF BLOOD AND BLOOD PRODUCTS

‘Shock‘). The vast majority of transfusion reactions are due to clerical errorsand can therefore be avoided by careful doublechecks. Note that acute haemolytic transfusion reactions do not occur in the very young infants. They also donot manifest delayed haemolytic transfusion reactions as they do not produce antibodies to allogenic erythrocytes. Isohaemagglutinins (the naturally occurring antibodies against other blood groups). which are responsible for acute haemolytic transfusion reactions, aredetectable in 4 0 % of infantsat age 6 months. Donor-recipient blood group compatibility red

Infant’s blood Compatible donor Compatible donor group cells

plasma

0 A B AB

AB, 0, A. B AB, A AB, B AB

0 0,A 0. B AB B,0,A,

Special considerations

Occasionally,strongly held parentalbeliefsagainstthe transfusion of blood or blood products make for potentially difficult management, particularly in the very preterm infant. Where possiblc it is desirable to be mindful of the parents’ wishes, as the parents will assume the care of theinfant followingdischargefrom the unit. Blood samplingfor diagnostic purposes should be reducedtotheminimum. Erythropoietinadministrationreducesthe need forlate transfusions. Where theneed fora blood transfusionis overwhelming and parents still object to ablood transfusion. it may be necessary to initiate legal proceedings, makingthe infant a ward of court. See ‘Special note’, p. 326.

Other blood products

I . Human albumin. This may be used tosupportthe circulating blood volume at 10-20mVkg (4.5% albumin), or for dilutional exchange (20-30mlkg). In oedematous states, 25% salt-poor albumin may be used to increase the plasma oncoticpressure.Some 4ml of 25% salt-poor albumin provides 1 g of albumin.

2. Freshfrozen plasma. FFP may be used for supporting the circulatingblood volume (10-20rnVkg),treating haemorrhagic states (e.g. DIC, vitamin K deficiency)and for dilutional exchange (20-30mVkg). 3. Cvoprecipirafe. This is used to replace clotting factors and correct bleeding states including fibrinogen deficiency (or fibrinogen < l It may therefore be used in haemophilia A,

a).

TRANSFUSION OF BLOOD AND BLOOD PRODUCTS325

von Willebrand's disease and dysfibrinogenaemia. A unit or bag is sufficient for an infant. An average of 80 units of factor VI11 activity is present in each 5-10ml bag. 4. Platelet concentrate. One unit of platelets (3050mYunit) raises the platelet count by50000. Give platelets to correct life-threatening bleeding or severe thrombocytopenia (platelet count 4o000/mm3), as one unit of platelets, or give up to 20mVkg.

Special note: All blood-products cany the theoretical risk of transmitting infection (and currently in the UK, new variant Creutzfeldt-Jakob disease, nvCJD). To August 1998. there had been 27 recorded deaths from nvCJD. The issue of plasma product safety arose when three of the first 23 nvCJD victims were identified as blood donors. This theoretical risk may be reducedbyusingplasmaproductsfrompopulationsnot affected by nvCJD (e.g. USA).A recent estimateof the risk of infection from transfusion of a unit of blood derived from a repeat whole blood donor gave a risk of 1 in 64OOO for HBV, 1 in 103000 for HCV, and 1 in 493 OOO for HIV (US data). A recent report has suggested an increased risk of mortality in critically ill patients who received human albumin for hypovolaemia or hypoalbuminaema.

Further reading Cohen AC, Manno C. Transfusion practicesin infants receiving assisted ventilation. Clinics in Perinatology, 1998; 25: 97-1 11. Dolan G. Blood and blood product transfusion. In: Lilleyman JS, Hann IM (eds). Paediatric Haematology. Edinburgh: Churchill Livingstone. 1992; 431-56. Hann IM, Gibson BES, Letsky EA (eds). Fetal and Neonatal Haematology. London: Baillihre Tindall, 1991. McClelland DBL (ed). Handbook of Transfusion Medicine, 2nd edn. London: HMSO Publications, 1996. Nathan G, Orkin SH. Nathan and Oski's Hematology of Infancy and Childhood, 5th edn. Philadelphia: W.B. Saunders, 1997. Vengelen-Tyler V (ed). Technical Manual of the Atnerican Association of Blood Banks. 12th edn. Arlington: American Association of Blood Banks, 1995.

Related topicsof interest Anaemia (p. 9) Bleeding disorders (p. 25) Blood pressure (p. 34)

Neonatal surgery (p. 200) Shock (p. 302)

326 TRANSFUSION OF BLOOD AND BLOOD PRODUCTS

TRANSPORT OF SICK NEONATES Of the approximately 150 million infants currently born each year worldwide, the vast majority have no accessto the level of neonatal care that they may require. Some infants may therefore require transfer to centralized or regional centres for specialized care. These include preterm infants, newborns with cardiacor surgical problems, and those with complex congenital malformations. In theUK, approximately 1% of all births (i.e. I O OOO infants) may require transfer in the neonatal period. Furthermore, 1 in 10 attempts to transfer may be unsuccessful due to lack of space (the majority being for infants of birthweight ~ 1 5 0 0 g )Infants . declined admission to centres offering a more appropriate level of care have a higher morbidity and mortality.However, inter-hospital transportationofhigh-risk infants is also fraughtwith potential dangers and complications which may further increase morbidity or mortality. It is now accepted that infants transferred under controlled conditions withskilled assistance have a reduced morbidity and mortality and have reduced requirements for intensive care. When time permits, the transfer of the pregnant mother to a more appropriate perinatal centre is associated with a more favourable neonatal outcome. However, transfer in utem with a mother in early labour is associated with increased risk of obstetric and maternal complications, including the unplanned delivery of an infant during transit. Neonatal transportation is therefore a serious undertaking, the success of which requires skilled personnel, appropriate equip ment, good communication and organi~ation. The goal of neonatal transport is to provide outborn infants with the same quality of care during transit as they would receivein a level 111 neonatal unit.

Equipment for neonatal transport

The equipmentused for neonataltransportshouldmeet the needs VLRW of infants through to the large term infants with surgical or medical problems. It should be easy to operate, light, robustandsecurelymounted to thetransportsystem. There should be a reliable battery providing ample back-up power for all vital equipment.

1. Transport incubator. This should be double-walledand able to provide a stable thermal environment despite variations in external temperature. 2. Ventilator. This should be simple to use yet reliable and preferably designed for transport use. It should allow visualization of the ventilator settings being used, and the oxygen concentration being delivered.

3. Drug and juid administration equipment. The 50ml syringe pump devices are probably the most appropriate and three to six may be needed.

4. Pulse oximeter:

5. Oxygenanalyser: 6. Suction devices. Theseshouldpreferablybebattery operated and with adjustable pressure.

7. Emergency equipment. For intubation,needleaspiration of the chest andchestdrain

insertion alongwithHeimlich

TRANSPORT OF SICK NEONATES 327

valves, hand ventilation, cannulation for i.v. access, a portable cold-light source and standard resuscitation drugs. 8. Medications. Some neonatal units maynothavethe following medications available at all times and it is preferable for the transport team to carry their own supplies: these include plasma, surfactant, dobutamine, dopamine, morphine, pancuronium, midazolam, and PGE, or PG$.

9. Mobile telephone. This maybeveryhelpfulin

case of

difficulties in transit.

Stabilization before transportation

The cornerstonesof ideal neonataltransportationarethemaintenance an optimal of temperature and normal or near-normal physiological parameters and the minimiration of unexpected adverse events. For a smooth transfer requiring minimal intervention en route, the infant must be stabilized before departure. Stabilimtion is the correction or treatment of processes that, left unaltered, may leadto a deterioration in the infant’s status. Infants transferred after adequate stabilization have a lower morbidity and mortality. Stabilization should assess the adequacy ofgas exchange and oxygenation, circulation (perfusion and BP), thermoregulation, acid-base balance and metabolic control.

Checks beforedeparture 0

0

During transportation

Secure airway and check position of endotracheal tube by radiographs. Assess adequacy ofventilation by the transport equipment by performing arterial blood gases prior to departure. If surfactant has been administered, wait for at least 30 min beforeperforming arterial bloodgases to determinethe need to reduce ventilatory support before the transfer. Assess adequacy of intravascular access sites and set up ‘reserve’ access sites if necessary. Check that BP and blood glucose are satisfactory. Ensure infant is well covered, insulated and warm, leaving only part of theface exposed for monitoring. Ensureanalgesiaandsedation will be adequateduring transport. Collect all therelevantmaternaland infant historical data and results ofrecentlaboratoryandradiological investigations. Inform your intended destination of your departure so that the receiving team are prepared for the infant, specifying any preparations which may be required in advance. rate, oxyUse full remote monitoring of temperature, heart gen saturation and BP. Avoid opening the incubator and exposing the infant to cold air.

328 TRANSPORT OF SICK NEONATES

Ensure ambulance cabin heating and lighting are adequate. Depending on the duration of the trip (e.g. 2 2 hours) or theOccurrenceof adverse events,additional monitoring (e.g. blood glucose measurements) may be required.

Checks on arrival

Take infant’s temperature and re-warm if hypothermic. Perform arterial blood gases and adjust ventilation andor correct significant metabolic acidosis accordingly. Check BP and augment it if necessary. Check blood glucose and correct hypoglycaemia if present.

Transport of infants ubowitzassessment. 19 lens examination, 20 nerve conduction studies. 20 large for, 165 small for, 165 Glanzmann’s disease. 27 Glucose-6-phosphate dehydrogenase deficiency, 173-174 Growth hormone, 30, 165. 168 Haemolysis, immune. 9 non-immune. 9 Haemolytic disease. 97-100 exchange transfusion in, 99 Haemorrhage. 9 fetal, 9 intra-abdominal. 6, 1 I intracranial. 4. I I , 16, 21 intraventricular. 7.21 priventricular, 21 pulmonary, 6,259-260 subaponeurotic, 21 subarachnoid. 21 subdural, 21.22 Haemorrhagic disease of the newborn. 27 Head size. 101-102 large head, 101 small head. 102 Heart murmurs in neonates. 103-104 innocent. 103 pathological. 103 Hepatitis hepatitis A, 179 hepatitis B, 105-107, 133, 179.245 immunization, 1 0 6 prophylaxis. 1 0 6 hepatitis C. 179 hepatitis D,179 Herniae, 108-109 epigastric. 109 inguinal, 108 umbilical 108 Hirsch5pmng’s disease. 1.49. 110-1 13 enterocolitis in, I 1 1, 112 intestinal obstruction in, 110 neuronal intestinal dysplasia and. I12 nitric oxide in. l IO rectal biopsy in. I I2

rectal manometry, 1 I O surgery for. I I2 HlV and AIDS, 114-1 17 vertical transmission, 1 l4 prevention of transmission, 115 Home oxygen therapy, 40.76,I18-119 Hydrocephalus, 120-121.204 Hydrops fetalis. IO, 122-125 Hyperammonaemia, 158 Hyperinsulinism. 30 Reckwith-Wiedemann syndrome and, 30 islet cell adenoma and, 30 ncsidiohlastosis and. 30 Hyperkalaemia, 266 Hypernatraemia. 4,239 Hyperoxia test, 65,66 Hypersplenism. 27 Ilypocalcaemia, 16 Slypofibrinogenaemia. 27 Hypotonia.126-127 Hypoxic-ischaemic encephalopathy, 16. 128-131 cerebral oedema in, 130 classification. 128 prognosis, 129. 131 seizures in, I28, I30 Immunization, 132-135 BCG. 132, 133.245 hepatitis A. 179 hepatitis R. 105. 133 varicella, 133 RSV. 134 Immunoreactive Uypsin, I, 198 Infants of diabetic mothers, 136-138 congenital anomalies in, I36 hypoglycaemia in. I37 Infection -general. 139-142 Infection neonatal, 143-146 MKSA, 145 RSV. 146 staphylococcal, 1 4 4 Infection perinatal. 147-150

-

Chlamydia rmchomaris. IS0

group B strrptocwcus. 148 herpes simplex, 149 listcriosis. 149 varicella-zosrcr, 149 Infection -prenatal. 151-155 cytomegalovirus. 152 herpes simplex. 153 IIIV. 155 parvovims B19, 155 ruhella. 151 syphilis, 153 toxoplasmosis. 151 varicella-zoster, 154 Inherited metabolic disease investigation and management, 156-160 blood investigations. 158 tissue biopsies, 159 specific therapies, I59 urine invcsrigations, 158 Inherited metabolic disease -recognizable patterns,

-

161-164

a,-anti-trypsin deficiency, 163 fatty acid oxidation defects. 161, 162

fructosaemia, 163 glycogenoscs, type I & 111, 162 I-cell disease. 163 MSUD, 161 non-ketotic hyperglycinaemia, 157. 162 organic acidurias, 161 peroxisomal disorders. 163 sialidosis 11, 163 tyrosinosis type I. 163 urea cycle defects, 162 Intrauterine growth restriction, 165-169 asymmetrical, 1 6 6 end-diastolic Bow in, l67 hypoglycaemia in. 1 6 6 necrotizing enterocolitis in. 167 polycythaemia in, 167 symmetrical. 166 Intubation, 170-172 complications of. 171 Jaundice, 173-176 kernicterus and. 174 pathological. 173 physiological, 173 prolonged. 173, 175 Jitteriness, 167, 177 Kasai operation. 178 Kleihauer test, I O Lactate, 3.29 Liver disorders, 178-181 biliary atresia. 175, 178 cholestasis. 174 disorders of bile metabolism. 180 infective hepatitis, 178 Lymphoid interstitial pneumonia, 116 Magnesium homeostasis, 88 Malformation Arnold-Chiari. 120 congenital. 70 cystic adenomatoid. 275. Dandy-Walker, 120 Maternal drug abuse, 182-184.295 HIV and, 182 neonatal withdrawal and, 183 seizures in. I84 Mechanical ventilation. 185-1813,

CPAP, 17. 185 HFJV, 59.239 HFOV. 59, 1X7.239 II’PV. 3.185 target blood gases, 185 trigger ventilation, 187 volume contmlled, 187 synchrony in, 186 Meconium aspiration syndrome. 189-191 asthma and. 1 9 0 ECMO in, 190 mortality in, 1 9 0 nitric oxide in, 190 surfactant in, 189 Meconium delayed passage, 245 ileus. I

INDEX 335

listeriosis and. 189 stained liquor, 189 Methylxanthines, l 7 aminophylline, 17 caffcine, 17 theophylline. 17 Multiple pregnancy. 192-194 Necrotizingentemolitis. 1. 117, 167, 195-1%. 223. 257 perforated. I. 6 pneumatosis intestinalis, 195 short bowel syndrome. 196 surgery for, 196 Neonatal diabetes mellitus, 32 Neonatal screening for inherited disease, 197-199 cystic fibrosis, 198 galactosaemia. 198 hacmoglobinopathies. 198 hypothyroidim. 197 phenylketonuria. 197 sicklc cell disease, 1 9 9 thalassaemia, 199 tyrosinacmia.198 Neonatal surgery. 200-202 Nerve palsy third nerve. 22 facial, 22 Erb's. 23 Homer's syndrome. 23 Klumpke's. 23 Neural tube defects. 203-205 agenesis of corpus callosum, 205 anencephaly, 204 cranial meningocele, 204 encephalocele. 204 holoproscncephaly,205 hydranencephaly, 205 megalencephaly. 205 meningocele, 703 microcephaly. 205 myelomeningocele, 203 spina hifida occulta, 203 Neurological evaluation. 206-209 Neummuscular disorders - muscular, 210-213 congenital muscular dystrophy, 210 congenital myopathies. 21 1 congenital myotonic dystmphy. 21 1 metabolic myopathies. 212 mitochondrial myopathies, 212 non-lysosomal glycogenoses, 212 Prader-Willi syndrome, 21 3 Neuromuscular dixordem - neurological, 214-217 anterior-horn cell disease, 715 SMA types I. I1 & 111. 215-216 neuromuscular junction disorders, 216 congenital myasthenic syndromes. 216 hypermagnesaemia. 217 infantile botulism, 217 neonatal myaqthenia gravis, 216 peripheral nerve disease, 116 giant axonal neuropathy. 216 inflammatory neuropathies. 216 metabolic neumpathies. 216 sensory neuropathies. 216 New variant Creutzfeldt-Jakoh disease. 280, 326

336 INDEX

Nitric oxide therapy, 218-230 HFOV and NO.220 methaemoglobin in, 219 nitrogen dioxide in, 9-19 PPHN and NO,219 Nutrition, 221-224 enteral, 222 total parenteral. 221 Oesophageal anomalies, 225-226 oesophageal atresia. 225 trachco-cesophageal fistula, 225 Oesophageal pH monitoring, 17.331 Orthopaedic problems. 227-229 congenital hip dislocation. 227 fractures. 228 talipes, 228 Ortolani's test. 227 Oxygenation index. 79,239 Patent ductus arteriosus. 230-233 diuretics in, 731 ibuprofen for, 232 indomethacin for, 231 surgical closure. 232 Pelizacus-Menbacher disease, 307 Periventricular leucomalacia. 234-236 cerebral palsy and, 235-236 perivcntricular echodcnsities. 235 Persistent pulmonary hypertension of the newborn, 237-240 ECMO in, 240 high frequency ventilation in, 239 intravenous vasodilators in, 239 NO in, 240 surfactant in, 239 Phosphate homeostasis. 88 Polycythaemia. 167. 241 hyperbilirubinaemia in, 242 hypoglycaemia in, 241 partial exchange transfusion in. 242 Postnatal examination. 244-246 Potassium homeostasis, 87 Pregnancy complications and fetal health. 247-252 antepartum haemorrhage. 247 gestational diahetcs, 136,251 oligohydramnios. 250 placenta praevia. 242 placental abruption, 247 polyhydramnios. 250 pre-eclampsia, 248 preterm labour, 249 preterm rupture of membranes. 248 prolonged pregnancy, 249 Prenatal diagnosis. 253-255 amniocentesis. 254 chorionic villus sampling. 254 fetal blood sampling. 254 pre-implantation diagnosis. 255 Pulmonary air Icaks. 356-258 pneumomediastinum, 1,257 pneumopericardium. 2.257 pneumoperitoneum. 257 pneumothorax, 3.6, 256 bilateral. 7 tension. 7

pulmonluy interstitial emphysema, 256 Pulmonary haemorrhage, 259-260 patent ductus arteriosus in. 259 surfactant in, 259-260 Pulmonary hypertension, 63 Pulmonary hypoplasia, 261-263 ECMO in. 262 NO in. 262 PPHN in. 262 Pulmonary lymphangiectasia, 275 Pyloric stenosis, 3, 332 Refractory hypoglycaemia, 30 hyperinsulinism and, 30 Beckwith-Wicdemann syndrome, 30 islet cell adenoma. 30 nesidioblastosis. 30 endocrine deficiency and, 30 cortisol deficiency. 30 glucagon deficiency. 30 growth hormone deficiency. 30 hypopituitarism. 30 inherited metaholic disease and, 30 treatment of. 32 diazoxide. 32 glucagon. 32 hydrocortisone, 32 octreotide. 32 somatostatin, 32 Renal and urinary tract disorders - nephrology. 264-269 acute renal failure, 265 nephrotic syndrome. 267 renal anery thrombosis, 267 renal tubular acidosis. 268 renal vein thrombosis. 267 Renal and urinary tract disorders - urology, 270-274 hydronephrosis. 27 1 hypospadias. 271 polycystic kidney disease. 270 posterior urethral valves, 270 renal agenesis. 270 urinary tract infection, 272 vesieo-ureteric reflux, 271 Respiratory distress, 275-277 Respiratory distress syndrome, 278-281 CPAP in, 280 mechanical ventilation. 280 prevention, 278 surfactant, 280 Respiratory failure, 3.276 Respiratory syncytial virus. 40, 146 ribavirin and. 146 RSVlG and. 40. 146 Resuscitation. 282-286 drugs in, 283 Retinopathy of prematurity. 287-290 classification, 288 cryotherapy. 289 screening, 288 Sedation and analgesia. 21.291-293 chloral hydrate. 292 diamorphine, 292 fentanyl. 201, 292 ketamine. 292 massage. 293

midamlam. 201,292 morphine, 2. 15, 196.201.291 Neonatal Infant Pain Score, 291 pancuronium, 293 paracetamol. IS, 292 suxamethonium, 293 vecuronium, 293 Seizures. 16, 21.22,242,294-297 benign neonatal sleep myoclonus. 296 clonic, 294 early infantile epileptic encephalopathy, 295 fifth day fits. 296 myoclonic, 295 pyridoxine dependency. 295 subtle. 294 tonic, 294 Sexual ambiguity, 298-301 congenital adrenal hyperplasia. 299 17-hydroxypmgesterone in. 299 salt loss in. 300 Shock, 302-303 Skin disorders, 304-306 aplasia cutis. 306 collodian baby, 305 eosinophilic pustular folliculitis, 304 epidermolysis bullosa. 305 erythema toxicum neonatorum, 304 harlcquin fetus, 306 incontincntia pigmenti, 305 infantile acropustulosis. 304 miliaria, 304 naevi. 305 neonatal acne, 305 neonatal lupus erythematosus, 306 transient neonatal pustulosis. 304 urticaria pigmentosa, 305 Sodium bicarbonate renal loss, 3. 4 Sodium homeostasis, 87 Stridor. 307-308 laryngomalacia, 307 subglottic stenosis, 55.307 tracheal compression, 307 vocal cord palsy, 307 Surfactant replacement therapy, 309-31 1 dosage, 3 I0 natural vs. synthetic. 310 patent ductus arteriosus in, 309 pulmonary haemorrhage, 309 prophylactic therapy. 309 rescue therapy, 309 Surgical emergencies. 312-314 gastroschisis. 312 posterior urethral valves, 270 torsion of the testis. 108. 313 strangulated hernia, 108 Syndromes adrenogenital, 271 Alport’s, 264 Angelman’s, 213 B-cell dysregulation. 30 Beckwith-Wiedemann, 30, 123.241.250 Bernard-Soulier. 27 Carhohydrate-deficient glycoprotein, 156 Cat eye. 5 1 Central hypoventilation, 40

INDEX 337

Cri du chat. 5 I Crigler-Najjar, 175 Diamond-Rlackfan, I I Down's, 49, 85. 1 IO. 126. 250 Dubin-Johnson. 175 Edward's, 50 fetal alcohol, 182, 184 Gilbert's. 175 HIJLLP, 248 Homer's. 23, 1 5 4 hyperviscosity, 241 hypoplastic left heart, 63.68 inspimtcd bile, 175 insulin resistance (syndrome X). 168 Kasabach-Merritt, 26 Killian-Pallister, 71 Klippel-Feil. 204 IAwrence-Moon-Riedl. I IO Lowc, 71 Meckel-Gruber. 270 meconium aspiration, 189-191 Moebias, 85 Ncu-L~xov~. 124 Patau, SO

polycythaemia-hyperviscosity,230 Potter's. 261 Prader-Willi, 85, 126. 213 prolonged QT,44 prune belly. 1. 193 Robert's. 205 Kotor.175 Sandifer's, 90 Scckel. 205 short-bowel, 1% Soto's, 101 staphylococcal scalded skin, 145. 305 TAK. 71 Turner's. 52 twin-twin transfusion. 193 Vater, 225 Waardenburgh. I IO Walker-Warhurgh. 210 Wiskott-Aldrich. 27 Wolf-Hinchhorn. 52 Wolff-Parkinson-White. 43 %Ilweger cercbrohepatorenal, 270 Zuelzer-Wilson. 1 IO Systemic lupus erythematosus maternal. I 1 neonatal. 306

338 INDEX

Tensilon test. 216-217 Thermoregulation. 315-316 Thrombocytopenia. 25. 196. 242 autoimmune. 27 alloimmunc, 26 DIC. 26 drug-induced, 97 hypersplenism, 27 IUGR, 16 polycythaemia, 26 sepsis. 26 Trace minerals and vitamins, 317-322 chromium, 317 copper. 3 l7 folic acid, 1 I , 203. 321 iodine, 3 17 iron, I l. 318 manganese, 318 molybdenum. 318 selenium. 319 vitamin A. 38. 320 vitamin R6.320 vitamin C. 320 vitamin D, 320 vitamin E, 1 I , 38.320 vitamin K, 92,25,27-28.245.321.399 zinc, 319 Transfusion blood, 4, IO blood p r o d ~ c t 323-326 ~, complications of. 323 exchange, 10.99 fetomaternal. 9 fetoplacental, 9 twin-twin. 9 Transport of sick neonates. 327-330 air transport. 330 equipment, 327 stabilization, 328

Tris-hydroxymethyl-aminomethane (THAM). 4. 302

Undescended testes. 2 I3 Volvulus. 314 Vomiting. 331-332 abdominal distension with. 331 bilious. 331 Werdning-Hoffman disease. 215 7aster immunoglobulin. 149